NG
I
MM
December 25, 2023 – January 14, 2024 ● SPECIAL ISSUE
LL
S
AU
KI
RE
CE
L
IA
OP
N
ME
N
P
E
TH
E
N
SO
G
RO
P
RA
’S
RA
S
IE
R
PA
NG
I
HT
G
RT
FI
PA
CH
R
EA
T
GEVI Y
S
S
N
IA
NS
RE
MA
AS
AR
N
TE
OD
N
CE
TH
PL
A
SP
L
EA
H
O
BL
THE
N
O
L
M
IS
V
TI
V
R
SE
T
EA
PR
RA
IC
B
T
AN
TS
E
D
CR
LA
EN
G
YO
D
I-
ISSUE
OL
H
ON
I
AT
AC
The immortality-obsessed frontier can feel like Silicon Valley
science fiction. Yet some of the latest anti-aging research could benefit
everyone, not just the true believers
ADVERTISEMENT
The Rise of Rwanda:
The Mining Opportunitiy
Each the size of a smartphone, freshly-processed
ingots emerge from the furnaces of Rwanda’s first
gold refinery at 99.99% levels of purity as a glistening
symbol of Africa’s evolving relationship with the
precious metals and rare earth minerals beneath
its soil.
At the Gasabo Gold Refinery, situated in the Special
Economic Zone of Rwanda’s vibrant capital Kigali,
there are plans to extend capacity to refine 220
kilograms of gold every day. The US$5 million facility
is a prime example of how Rwanda’s introduction of
modern and sustainable mining, refining and smelting
techniques is unlocking the potential of Africa’s
mineral exports.
Rwanda’s mining sector generated US$772 million
in foreign exchange in 2022, double the figure for
2019. Geological mapping has identified its extensive
deposits of rare earth metals including wolframite,
cassiterite and coltan. Its gemstone portfolio includes
amethyst, blue sapphire and ruby. And as well as
exploring and excavating its own natural resources,
Rwanda is seizing the opportunity to be a continentwide processor of metals and minerals.
US$772 million is generated from
Rwanda’s mining sector in 2022,
double the figure for 2019.
The Gasabo plant, the result of a private joint
venture backed by foreign investors, is positioned
to become the epicenter of gold refining services
across Africa, a continent that produces 870
metric tons of gold annually, more than 20% of
global output. In the north of Kigali, another stateof-the-art facility, the LuNa Smelter, is boosting
the entire metallurgical and mining sector of East
Africa with its ability to process sustainablysourced and premium-quality tin.
A F R I CA
RWAN DA
A DVERTISEMENT
Increasing demand for Rwandan
minerals in technology, defense,
medical and green energy sectors.
$
$
7.5
609
MILLION
MILLION
Worth of joint venture
is signed for Rwandan
lithium deposits.
Of mineral export earnings
by Rwandan mining in the
first six months of 2023.
Rwanda has established a Regional Certified
Geochemical Laboratory to conduct in-country mineral
sample analysis, reducing research costs for investors
and improving efficiency within the sector. The country
is also investing in cutting-edge mineral exploration
techniques to build a deep repository of robust primary
data on its Prospective Target Areas (PTAs), enabling
FDI investors to make informed decisions on strategic
investments in new mining areas.
The University of Rwanda’s School of Mining &
Geology is supplying a talent pool of trained Rwandan
geologists and engineers, who bring innovative ideas
and a belief in environmentally-conscious modern
mining techniques. The result is that a sector that once
relied on artisanal methods is being transformed. Yet
mining equipment companies are rare in the region
and clear opportunities still exist for foreign investors
to support Rwanda’s transition to semi-mechanized
mining and ultimately a fully-industrial framework.
Thanks to the growing availability of precision
mineral data and new levels of expertise in the sector,
Rwanda’s mining sector is expanding fast. In the
first six months of 2023, its mineral export earnings
reached US$609 million, putting it on course to reach
its target of US$1.5 billion annual mineral export
earnings by 2024, according to the RMB.
But Rwanda’s ambition goes much further. It believes
it can be a value-addition hub for mining across
Africa. It is already a regional leader in refining
gold and tantalum. It is unrivalled in smelting tin.
But unexploited opportunities remain in developing
similar plants for processing tungsten and lithium. It
could also become a regional center for cutting and
polishing gemstones, a nascent sector with a potential
that glitters in the form of unexcavated Rwandan
aquamarine, amblygonite and quartz.
As Rwanda digs for a better future, it is unlocking the
earth’s natural treasures all over Africa.
In the south of Rwanda, the PowerX Tantalum
Refinery is taking Rwandan coltan ore and separating
it into tantalum and niobium, two valuable transition
metals used in the technology, defense and medical
sectors. The green energy revolution is escalating
demand for the minerals found in Rwanda, especially
lithium and the three T’s (tantalum, tin and tungsten).
The global price of coltan grew from US$33.7 per kilo
in 2019 to US$48.82 in 2022. In August, global mining
group Rio Tinto signed up to US$7.5 million joint
venture to explore Rwandan lithium deposits.
Rwanda has a long mining history. The first mineral
explorations were carried out by Belgian companies
a century ago. But the sector’s impressive recent
growth is a consequence of bold investment in its
infrastructure and a strong regulatory framework
enforced by the Rwanda Mines, Petroleum and Gas
Board (RMB), which inspects facilities and oversees
licence compliance.
GET INVESTED
IN A BREEZE.
Even in these market conditions,
iShares Core ETFs make it easy
and affordable to be invested so
that you can be ready for that
next market upswing.
Get your share of progress.
Visit www.iShares.com to view a prospectus, which includes investment objectives, risks, fees, expenses, and other
information that you should read and consider carefully before investing. Investing involves risk, including possible
loss of principal. This information should not be relied upon as research, investment advice, or a recommendation regarding any products, strategies, or any security in
particular. This material is strictly for illustrative, educational, or informational purposes and is subject to change. Buying and selling shares of ETFs may result in brokerage
commissions. Prepared by BlackRock Investments, LLC, member FINRA. © 2023 BlackRock, Inc. or its affiliates. All Rights Reserved. BLACKROCK and iSHARES
are trademarks of BlackRock, Inc. or its affiliates. All other trademarks are those of their respective owners. iCRMH0523U/S-2879346
A WORLD FULL OF CENTENARIANS
Half of today’s 5-year-olds in wealthy
countries are expected to live to 100. As
researchers discovered in developing a
new map for aging, society isn’t prepared
12
LONG LIVE SILICON VALLEY
Growing old gracefully isn’t enough for
those who want to be immortal. Meet
the Biotechs, Wellness Obsessives and
Radicals devoted to solving the problem
18
LEARNING FROM LAB RATS
The rodents who are so important to
medical research typically don’t reach
old age. An unsung group of elderly mice
and rats is the exception
24 32 38
INSIDE A SECRETIVE LONGEVITY LAB
Retro Biosciences, a startup with
$180 million from Sam Altman, has
a simple and audacious goal: Add
10 good years to your life
THE ISLAND OF BETTER GENES
Biohacker Bryan Johnson travels to
a beachside resort in Honduras for a
supposed fountain-of-youth injection.
It is, of course, unapproved
DECEMBER 2023
8
TABLE OF CONTENTS
THE LONGEVITY ISSUE
BUZZWORDS FOR SKINFLUENCERS
Dermatologists warn that consumers
should be wary of scientific-sounding
skin-care routines on, say, TikTok.
Sunscreen, anybody?
5
PAUSING MENOPAUSE
A woman’s biological clock is a fact
of life, but drugs may soon change
that—extending fertility, yes, and also
improving human health
A HANDBOOK FOR BETTER AGING
You’ve got questions about the golden
years, and we’ve got answers. How to
downsize, make new friends or even
take a lover
SO YOU WANT TO KEEP WORKING?
Over the past seven decades, these jobs
have had the most employees older than
65, including farmers, clergy, school bus
drivers and funeral directors
THE LONGEVITY ISSUE
40 50 56
TABLE OF CONTENTS
DECEMBER 2023
THE LONGEVITY ISSUE
6
THE LONGEVITY ISSUE
COVER TRAIL
58 66
FIGHTING PARKINSON’S
An alliance between Google founder Sergey Brin
and actor Michael J. Fox is putting $350 million
annually toward halting the progression of the
neurological disease
“This week’s issue is
all about the human
life span and how
we’re trying to expand
its outer limits.”
“To infinity and
beyond!”
“Actually, that’s kind
of accurate. What do
you have for me?”
“I’m thinking babies
that are gonna live
to 200!”
“Too Colors mag.”
“Perhaps we do
Möbius strips of
lined-up people?”
HOSPICE BY ALGORITHM
It’s difficult for doctors to decide when a patient
should stop treatment and start end-of-life care.
What if artificial intelligence could help?
6880
A SUPERCOOL EXPERIMENT
At the Alcor Life Extension Foundation, more than
200 human bodies or heads are preserved at -321F.
What does their $200,000 fee buy? Science fiction
or something real?
How the cover
gets made
LESSONS OF THE WORLD’S OLDEST BUSINESSES
Some products and services never go out of
style—truly. But if a 1,200-year-old restaurant
can pivot to serve brunch, there’s hope for
companies everywhere
“Getting warmer!”
“OK, how about a
beautiful still life of
objects representing
different aspects of
longevity culture?”
“Getting somewhere,
but too complicated.”
“OK, fine. People
in ice cubes!”
“Sold!”
Cover:
Photograph by Ian
Loring Shiver for
Bloomberg
Businessweek;
set design: Kelsi
Windmiller
ADVERTISEMENT
BUILDING A GLOBALLY TRUSTED
CybersPACE
“A lot of people think
cyberspace is the wild,
wild west, where there are
no rules. That is not true.
The digital domain is a
shared one – we must
collectively steward this
rapidly changing space
and ensure it remains
secure, accessible and
beneficial to all.”
Amid the high stakes of generative AI
and the convergence of ethics, privacy
and governance, the words of David Koh,
Chief Executive of the Cyber Security
Agency of Singapore (CSA), were a
unifying call for the 12,000 global
policymakers, business leaders and
industry experts who gathered at the
largest edition of Singapore International
Cyber Week (SICW) from October 16 to
19, 2023.
An Emerging
Digital Order
Across key events including the
International IoT Security Roundtable,
the ASEAN Ministerial Conference on
Cybersecurity and High-Level Panels,
SIC W 2 023 dre w u n p a ra l l e l e d
participation from more than
80 countries – highlighting the
fu n d a m e n t a l , s h a re d b e l i e f i n
cybersecurity cooperation as a
powerful counterweight to turbulent
geopolitics and insular worldviews.
“Singapore shares the view of many
other states and organizations: that the
digital domain should be open, secure,
stable, accessible, peaceful and
interoperable. To harness digitalization
a s a f o rc e f o r g o o d , w e m u s t
collectively build the right frameworks
and scaffold it with shared rules,” noted
Heng Swee Keat, Singapore’s Deputy
Prime Minister and Coordinating Minister
for Economic Policies, in his opening
keynote address.
A Common
Denominator
Whether fostering partnerships across
borders and sectors, developing shared
rules and norms of behavior, or creating
new capacities to guard against cyber
threats, trust is fundamental in building
an emerging digital order.
“Increasing trust between states is
essential,” noted Izumi Nakamitsu, the
United Nations’ Under-SecretaryGeneral and High Representative for
Disarmament Affairs. “To address
concerns of trust and mistrust linked to
the digital space, the international
community must better regulate and
manage our digital commons as a
global public good.”
Borderless
Cooperation
As the digital economy surges to more
t h a n 1 5 % of gl ob al GDP, d i gi t al
economy agreements such as the
Digital Economy Partnership Agreement
between Singapore, Chile and New
Zealand, as well as the recent
commencement of negotiations for the
ASEAN Digital Economy Framework
Agreement, are crucial in strengthening
multilateral cooperation and digital
integration.
Likewise, international cooperation is
crucial in resolving the cybersecurity
skills gap. Forged on the sidelines of
SICW 2023, CSA’s partnership with the
United Kingdom’s Department of
Science, Innovation and Technology
aims to strengthen the countries’
cybersecurity workforces through the
alignment of professional skills and
competencies.
The Centrality
of Big Tech
Equally crucial is building trust
between governments and the tech
industry. As Jen Easterly, Director
of the Cybersecurity and
Infrastructure Security Agency of
the United States, said, “to shift the
paradigm, we need to transform
these public-private partnerships
i nt o
real - t i me
op erat ional
collaboration,” characterized by
equal partnerships, scalable
platforms, and sharing as second
nature.
Such public-private initiatives
include the inking of CSA’s new
partnerships with Microsoft and
Google on national cyber defense
through cyber threat intelligent
sharing, exchanges on emerging
and critical technologies, as well as
capacity building efforts – with the
ultimate aim of bolstering public
trust in the digital domain.
A Unified Goal
Now in its eighth year, SICW has
established itself as the leading
global platform for understanding
and navigating the benefits as well
as risks of the digital revolution, and
ensuring a safe, inclusive
cyberspace for all users.
As Singapore’s Senior Minister and
Coordinating Minister for National
Security Teo Chee Hean summed
up, “the challenge of building and
maintaining trust in the digital
domain is complex, but it is
imperative that we work on it
together. I hope that we will
collectively achieve a better
understanding of each other’s’
perspectives, recognize our shared
interests in cyberspace, and work
towards building the trust we need
for a digital world and a better
future.”
AGING IS NG
CHANGI
The lasting effects of spending two years studying longevity at Stanford
By Karen Breslau Photographs by Julie Glassberg
CREDITS CREDITS CREDITS
JAAAAAANUARY 2023
TEKAY SUBJET MATTER
6.6/8 CURABITUR CONSEQUAT NISI EU EST. PELLEN VESTIBULUM LACUS EGETULPARCHITIO. ALIQUIS ALIQUE LAUT QUIBUSA COREIUNTIUM APERIT
6.6/8 CURABITUR CONSEQUAT NISI EU EST. PELLEN VESTIBULUM LACUS EGETULPARCHITIO. ALIQUIS ALIQUE LAUT QUIBUSA COREIUNTIUM APERIT
CENTENARIANS
DECEMBER 2023
9
THE LONGEVITY ISSUE
A
t the end of 2020, the Stanford Center on Longevity
commissioned me to compile its research into a
report for a general audience. The center’s mission is to accelerate scientific discoveries that
improve the likelihood and quality of longer lives and to
change cultural norms around the economic and social
contributions of older adults, hence the interest in sharing its work with the public and policymakers. Specifically,
researchers there were studying what life would look like
when people routinely lived to 100. At the time, I was a
freelance writer with no expertise on the topic beyond
having a grandmother who reached 102—vibrant, opinionated and engaged with the world. But the assignment was
a welcome diversion from a reality in which so many
lives were being cut short.
I assumed, given that I was working for a center on
longevity, that I’d be writing about old people. But as
I dug into its scientific papers, as well as reports from
the Centers for Disease Control and Prevention and
the United Nations, it was the data about kindergartners that stood out. According to some models, half
of today’s 5-year-olds in the wealthiest countries are
projected to reach 100. Despite gun violence and epidemics of obesity, diabetes and opioids—and accounting
for disparities in race, gender and income—life expectancy in the US is still going up. While Covid-19 caused
a short-term setback, from 79 in 2000 to 77.5 in 2023,
according to the CDC, models suggest life expectancy
will approach triple digits this century.
For almost two years I worked with investigators who
were tasked with designing a society where future centenarians would be healthier, more economically productive and more socially engaged than they are today.
Laura Carstensen, a renowned psychologist, longevity
scholar and founding director at the center, led the team;
it included biologists, doctors, educators, sociologists,
climate scientists, urban planners, product engineers,
entrepreneurs, economists and experts in financial
services, fitness and public health. Carstensen’s challenge to us was, to put it in academic terms, ginormous:
Reengineer the entire human experience to chart a “new
map of life,” as she put it, to “change the future of aging
and make longer lives better at every stage.” It would
be a handbook policymakers, employers and investors
could use to prepare for risks and opportunities while
also offering a modern script to influence the public’s
understanding of longevity. I was used to writing complex narratives. Maybe not this complex.
The plotline we uncovered is that even though the
centenarians of the future are here, society isn’t set up
to handle people living routinely into their 80s, 90s and
beyond. We’re not invested in the technologies and
therapies to help people stay healthy and independent
as they age, and we haven’t reconsidered how to adapt
work so companies can make better use of the skills and
experience of older employees.
We still think about life in linear stages: education,
work, retirement. It’s an outdated framework from the
late 20th century, when it made sense to start school
at age 5, enter the workforce or get a college degree in
one’s early 20s, start a family, work until 65—and then
enjoy mall walking. Living to 100 demands a more flexible path. Just about everyone will be in the workforce
much longer, changing not only jobs but also careers
several times over the course of a working life that may
span six decades. If you’re not familiar with the term
“midlifeship,” it’s exactly what it sounds like: an internship for people in mid-career to help facilitate new roles
as industries change in response to artificial intelligence
and whatever currently unknown and potentially apocalyptic technology everyone will fear next. In a society where reskilling and upskilling are as important as
bachelor’s degrees, educations won’t be defined solely
by the formal institutions conferring them.
It should become standard practice, the team
agreed, for there to be recurring phases of earning and
non- earning years, so that milestones around education, career and family don’t have to be so front-loaded.
This flexibility could relieve pressure on younger workers, especially women, when the demands of the peak
career-building years collide with the demands of
starting a family. It would also ease the tensions that
drive older workers into early retirement, when what
they really need is just a respite to deal with health
issues or caregiving. Preventing needless losses of
income, payroll taxes and productivity will take changes
to safety net programs such as Medicare and Social
Security, which penalize recipients who dip back into
the 9-to-5.
The Stanford team proposed several aspirational
solutions to funding longer lives, such as financial products similar to 401(k)s that would let people save for
non-earning intervals. Another idea: Financial markets
could develop longevity bonds to distribute the risks
associated with longer lives faced by entities such as
benefit plans or long-term care insurance providers
across wider markets. As people remain healthier and
more productive over a longer life, the bonds would
deliver greater returns. (The researchers weren’t asked
to project costs for their whiteboard proposals.)
In some ways, this future is already here. As boomers age, US workers 65 and older are projected for the
first time to account for the largest and fastest increase
in the labor force, according to the Bureau of Labor
Statistics. Research by Carstensen and others shows
that many knowledge workers can stay productive
into their 70s and 80s. Their emotional intelligence,
problem-solving skills and life experience can compensate for advantages younger workers have grasping the
latest tech. At the same time, teams that are more age-
CENTENARIANS
DECEMBER 2023
diverse outperform those that are less so. With
as many as five generations alive together for
the first time in history, there’s a lot of room for
intergenerational learning.
I
f working for various stretches over the course of
more than a half-century with eager up-and-comers who don’t get your pop culture references
doesn’t sound appealing, yeah, we get that. But
I think about my 40-year-old self and what I
would’ve given to have spent more time with my kids and
less time gnashing my teeth as I tried to fulfill the dual
responsibilities of parenting and career. This first issue of
Bloomberg Businessweek dedicated to longevity looks at
the promises—and potential perils—of experimenting with
our future. And at a time when our understanding of the
world is shaped by war, climate change and the long tail
of a global pandemic, that future may even be brighter.
Ellen Huet writes about anti-death activists (page 12)
who call themselves “Immortalists” and have made a
personal commitment to try to live forever. “Dying is
bad,” one says. “This is something humanity doesn’t
take seriously enough.” Cara Giaimo looks at rodents
that are allowed to grow old to test how effective certain life-extension methods may be for humans (page 18).
Ashlee Vance profiles Retro Biosciences, a company that’s
10
trying to give every human 10 additional years of quality
living (page 24), and Minicircle Inc. (page 32), the startup
behind an injectable gene therapy that it calls humanity’s best hope for “extreme longevity.” (The US Food and
Drug Administration has, uh, not endorsed this claim.)
Kristen V. Brown investigates the intriguing possibility
that anyone with ovaries may one day be able to control
the onset of menopause (page 40), and Robert Langreth
writes about whether scientists are getting closer to a drug
that stops the progress of Parkinson’s disease (page 58).
And if you have $200,000, Alastair Philip Wiper explains,
your body can be cryogenically preserved after death
(page 68). Why would you want to do this? Well, let’s
not crush anyone’s dreams right now.
The New Map of Life, the 82-page report the center
published in 2022 and presented at conferences, made
its own forays into what might read today as science
fiction. “Be prepared to be amazed by the future of
aging,” the report said. “As they age, future centenarians might have electronic tattoos functioning as ‘smart
skin’ to monitor heart, brain and muscle function for
abnormal activity or disease. These bio-integrated electronic devices, thinner than a human hair and as supple
as skin, could supplant today’s wearable technologies
(smart watches, Fitbits and the like) and be capable of
preventing an epilepsy attack, resetting an irregular
heartbeat or sending biometric data to be analyzed by
a doctor for early intervention.”
More immediately, some of the project’s findings have
made their way into a course Carstensen co-teaches at
the Stanford Graduate School of Business. The class
looks at the growing population of adults older than 50
not as a net drag on society, ruinously depleting health
care and entitlement programs, but as an untapped labor
resource. In the US, this diverse and relatively affluent
cohort accounts for 50% of consumer spending and 83%
of household wealth, mostly through homeownership.
Which means there are business opportunities associated with everything from travel and leisure to end-of-life
PATRICK COTTEREAU, 60,
SHARES LUNCH AND DANCES
WITH LIESEL ABROMONT, 97,
AT HER HOME NEAR PARIS EVERY
TWO WEEKS. A PROFESSIONAL
DANCER, HE WAS HIRED BY
ABROMONT’S DAUGHTER AFTER
HER FATHER DIED.
BRIGITTE BOURBAN,
66, WHO LIVES
IN PARIS, GOES
DANCING ON SUNDAYS
AND MONDAYS FROM
2 P.M. TO 9 P.M.
AT THE FAMOUS
NIGHTCLUB DUPLEX.
care and financial planning—and which
helps explain why the center’s research
is sponsored in part by the AARP and
the Financial Industry Regulatory
Authority as well as corporate affiliates
Bank of America Corp. and Finance
of America Reverse LLC, a reversemortgage lender. (Reverse mortgages
let older homeowners borrow money
against the equity in their homes.)
Spending two years immersed in
the possibility of living to 100 changed
my perspective about my own life
and career. I’m now bureau chief for
Bloomberg News in California, where
age and power are often the subtext
as the political generation includDANCERS TAKE A
ing Governor Gavin Newsom and BREAK AT FAMED
US Senate candidates Adam Schiff DANCE HALL CHEZ
GÉGÈNE NEAR PARIS.
and Katie Porter tries to take a stage
that’s been dominated by older leaders including Nancy
Pelosi and the late Dianne Feinstein. Her recent death
made plain the ways in which even the highest profile
among us can’t escape the limits of longevity. My kids
are now young adults, and whether any of us will match
my grandmother’s 102 years, a miracle for someone born
in 1906, can’t be known. But it’s not crazy to imagine it. <BW>
11
GISÈLE LE BOULANGER, 75, HAS
BEEN A REGULAR AT DUPLEX FOR
15 YEARS—IT’S WHERE SHE MET
HER CURRENT BOYFRIEND.
The photos accompanying this story are from a project called Stayin’ Alive.
Julie Glassberg got the idea for it about 15 years ago, when she was at a
famous brasserie in Paris, La Coupole, which organizes afternoon thés
dansants (dancing teas). “A very chic old lady, quite elegant, came to talk
to us. She told us she’d come to the thé dansant every Sunday. She loved
to dance, and she’d also meet lovers!” Glassberg wrote in a short essay
explaining her project. (“Some bring their lovers. Some are single and
meet lovers. Some are married and meet lovers. You’ve got everything,”
she clarifies.) The project, produced as part of a national commission with
the support of the Bibliothèque nationale de France, includes seniors who
attend thés dansants throughout the country. Glassberg says her goal is
to expand her portfolio to include older people with diverse interests in
France and other countries.
THE LONGEVITY ISSUE
JEAN-PAUL DURET,
83, WHO LIVES NEAR
AVIGNON, HAS BEEN
DANCING SINCE HE
WAS 15 AND NOW
GOES FREQUENTLY TO
CRYSTAL, BATACLAN
AND OTHER CLUBS.
Ideas about living better, longer or forever have taken hold in much of the technology
industry. Here’s what that means
By Ellen Huet Photographs by Ian Loring Shiver
S
R
EVE
CREDITS CREDITS CREDITS
THE BE
LI
THE LOOOOOOOONGEVITY ISSUE
CREDITS CREDITS CREDITS
JAAAAAANUARY 2023
TEKAY SUBJET MATTER
made a personal commitment to try to live forever, and
they believe defeating aging should be a top priority for
both research dollars and social activism. They carry
around posters with mantras such as “Death is unacceptable,” “Death is boring” and “Stay alive,” all of which
made appearances this fall outside the historic Ferry
Building overlooking San Francisco Bay. One particularly devoted volunteer took the idea of permanence to
heart and got the words “SAY FOREVER” tattooed across
the front of his neck. “Dying is bad,” Egorova says. “This
is something humanity doesn’t take seriously enough.”
The Immortalists may sound more like the Merry
Pranksters than a serious lobby, but they embody a strain
of tech industry culture that’s taken hold in the occasional gaps between conversations about artificial intelligence and crypto. Different circles in the Bay Area and
other tech hubs are looking for methods to cheat death,
from popping supplements and pipetting solutions in a
lab to trying to digitize their consciousness or freeze their
brain to be revived later. (They hope.) The underlying
belief is that technology could someday transcend our
ultimate biological destiny. Or as influential investor and
provocateur Balaji Srinivasan’s X bio puts it: “Immutable
money, infinite frontier, eternal life.”
What distinguishes this obsession from a typical
midlife crisis is the scale of the money behind it. Jeff
Bezos, Sam Altman, Larry Ellison, Larry Page and other
tech titans have pledged hundreds of millions of dollars toward companies pursuing longer life. Partly as
a result, immortality-obsessed people in the industry
have begun to view radical life extension as a near-term
option. Some are, by day, investors or researchers in AI.
Others are cryptocurrency winners with fiat money to
burn. Ethereum co-founder Vitalik Buterin has emerged
as a flag-bearer for longevity advances—he’s donated
millions of dollars to research organizations and posts
things like: “Aging is a humanitarian disaster that kills as
many people as WW2 every two years.” Robert Nelsen, a
hedge fund manager who has a stake in longevity-focused
THE BIOTECHS
These folks are developing
drugs they plan to submit for
formal approval by the FDA
and aim to have available behind
the pharmacy counter within
the next decade
SET DESIGN: KELSI WINDMILLER
CULTURE
DEECEMBER 2023
THE LOOOOOOOONGEVITY ISSUE
W
hen a chipper person with a clipboard
approaches you on the street in San Francisco,
you can usually expect the inquiry to be about
one of a few public-policy goals. Do you have
time to talk about abortion rights? Housing? Online gambling ballot initiatives? These days, though, you might
also hear a question that’s both more grandiose and more
personal, the kind of thing you wouldn’t expect to hear
from someone who looks like they want your signature.
The question: How long do you want to live?
One Saturday in August, Anastasia Egorova, the
37-year-old chief executive officer of a longevity
research nonprofit, organized two dozen volunteers
in San Francisco and 10 other cities to collectively get
answers from almost 200 passersby. Many respondents pegged their desired life span at somewhere from
80 years (roughly the US average) to 120 years (close to
the global record). Egorova’s clipboard-toting volunteers
in São Paulo and Toronto heard much the same that day,
as did volunteers in Haifa, Israel, and Malmö, Sweden.
Few people rose to the challenge posed by the merch
many of the clipboarders were wearing. All of the hats,
T-shirts and stickers read, “Say Forever!”
Egorova and her fellow anti-death activists, a bunch of
scientists and longevity enthusiasts who call themselves
“Immortalists,” argue that a good and rational person
should want to live as long as possible. While they recognize the existence of the chronic pain and unspeakable
traumas that make for strong counterfactuals, they’ve
T
o keep track of the different factions, we’ll
give them some nicknames. In one corner
are the Biotechs, the most buttoned-up of
longevity researchers. They’re developing
drugs that they plan to submit for formal
approval by the US Food and Drug Administration and
that they aim to have available behind the pharmacy
counter within the next decade. Some of these medications are meant to promote autophagy—a cell’s ability to recycle accumulating molecular junk—or clearing
out senescent cells, which have aged faster than other
cells and can no longer replicate.
CULTURE
DEECEMBER 2023
It’s early enough yet for these drugs that one of the
most promising treatments targets dogs rather than people. “We started with big dogs because a Great Dane has
an average life span of 6 to 9 years, and it’s starting to go
gray even at age 3 or 4, so you can see it much faster,”
says Celine Halioua, the CEO of Loyal. Those accelerated
dog years make it much more practical to run clinical trials on aging, as opposed to a 50-year trial for human longevity. Halioua’s idea is to give dogs more healthy years
by reducing the release of growth hormones, which are
correlated with faster aging in larger breeds. She’s sensitive to scaremongering about zombie dogs and stresses
that her goal is “healthy life span extension” for a cherished pet. “We talk about Fluffy being able to chase the
ball longer, being excited when you’re home and not
being stiff when she gets out of bed,” Halioua says. Dogs
are a “nonthreatening” way to introduce the public to
the idea that the biology of aging is malleable, she says.
A 15-year-old dog doesn’t evoke all the fears of playing
God that a 150-year-old human does.
Then there are the Wellness Obsessives. These are
people fed up with the medical establishment’s focus
on acute care instead of preventive care, and they’re
keen to try supposedly proactive therapies that are
often ignored or dismissed as snake oil. (Think Braintree
Payment Solutions LLC founder and unofficial Bloomberg
Businessweek mascot Bryan Johnson, who’s spending millions of dollars a year to make his middle-aged body work
more like a teenager’s.) While some of their experiments
are pretty far out, the WOs are still considered relatively
conservative in longevity circles. They’re focused on zealously evaluating their bodily functions so they can make
incremental improvements. Like the Biotechs, they tend
to say some version of “health span” a lot.
“You are more in control of your health than you
think,” says Martin Tobias, a venture capitalist and the
former CEO of Upgrade Labs Inc., a chain of facilities
specializing in gadgets such as an oxygen trainer and an
AI-enhanced stationary bike. “If you’re the CEO of your
own health, you can get outcomes that are not usually
delivered by the traditional medical system.” Tobias,
who’s about to turn 60, says he wants to make sure he’s
around when his youngest daughter, now 8, is graduating from college. To get there, he’s trying some stuff that
wouldn’t seem out of place at a Goop retreat. His Seattle
garage is packed with $500,000 in equipment, including two saunas, an infrared light bed, an electromuscular
stimulation suit and a cryotherapy chamber. He takes
cold plunges, flies to Central America to get injections
of stem cells and undergoes treatments to lengthen his
telomeres, chromosomal proteins that shorten with age.
Tobias and others like him believe that in the pursuit
of slowing their own clock, it’s worth burning money on a
dozen experimental treatments even if most don’t work.
Big names in this world include physician Peter Attia,
geneticist David Sinclair and futurist Peter Diamandis.
It’s tough to know whether any of it’s working, given that
the biomarkers thought to measure a person’s “biological
age” are still poorly understood. Still, Tobias is doing the
work and analyzing the results, and he says he’s seeing
15
THE LOONGEVITY ISSUE
biotech Altos Labs Inc., takes almost a dozen drugs a day,
including rapamycin, which has been shown to increase
life span in mice. Venture capitalists are pivoting to focus
on longevity companies, and tech connectors are launching longevity-focused fellowships to entice newcomers
to the field. Most of these crowds are united by technooptimism and a belief that they’re privy to a hidden truth.
Contrarianism is the norm, says Amol Sarva, one of
the investors eager to fund advances in the field. He says
the industry is a mix of “graybeard wizards” proclaiming mystical-sounding futures, more conventional biotech experts focused on science, the “Peter Pan types”
who project youth and the “cyborg types” talking about
a future in which human consciousness transcends the
fleshy body. Sarva, who used to run the WeWork clone
Knotel Inc., has raised a $100 million fund with a partner to invest in longevity-related companies, with checks
already written to those using AI to better treat cancer
and stem cells to create biology-powered computers. He
compares the energy of the longevity scene to that of the
Homebrew Computer Club, a disco-era gathering that
fueled the birth of the personal computer and Apple Inc.
Although it can be easy to reduce the various longevity efforts to one big blob of existential dread powered by money and fragile male egos, the community
includes cliques with very different aims. Some are
focused on extending the average human life by a modest range. Others are more conservative, promising only
to add more “health span,” meaning healthier years
within a natural time frame. And some go fully eternal,
promising—with typical Silicon Valley restraint—to build
their own sovereign-ish state where they plan to master
and defeat death. “We’ve accepted aging and death as
inevitable, and now there’s a very good reason to believe
they will be solved,” says Adam Gries, an investor focused
on longevity. “The only question is when.”
THE WELLNESS OBSESSIVES
These are people fed up with the
medical establishment’s focus on
acute care instead of preventive
care, and they’re keen to try
supposedly proactive therapies
that are often ignored or dismissed
as snake oil
THE LOONGEVITY ISSUE
16
improvements that are bringing him some peace, along
with a sense of control. “My telomeres are measuring
38 years old,” he says.
Both the Biotechs and the Wellness Obsessives are
at pains to emphasize that they still expect to die. For
the Radicals, that’s loser talk. Patrick Linden, a philosopher who wrote a book called The Case Against Death,
calls the acceptance of mortality a “fallacy” meant to
“protect yourself from the tragedy of wanting something you can’t have.”
The Radicals’ cause began to reach the mainstream in
the mid-2000s. In 2005, Nick Bostrom, an influential AI
theorist, wrote a fable in which death takes the form of a
tyrannical dragon that terrorizes a kingdom, demanding
a constant stream of sacrifices, until a brave king spends
vast sums over many years to develop a missile that kills
it. (A video version of the fable, posted on YouTube far
more recently, has about 10 million views.) Around that
time, British researcher Aubrey de Grey, whose foot-long
beard gave him a bit of a Merlin vibe himself, became
the public face of a fledgling longevity movement. De
Grey said in a BBC interview that the first person who’d
live to 1,000 was probably already alive, then delivered a
TED Talk about why humanity should devote resources
to fighting aging. He argued that once we’re able to repair
aging damage at a faster rate than we age, we’ll reach
“longevity escape velocity,” where age-related mortality
keeps receding farther and farther away.
This possibility of living much longer—or forever—
has inspired bioethicists and philosophers to ponder the
prospect’s unexpected consequences. It’s an isolating field
of study. “If I go to the hairdresser and I tell them what
I’m working on, the immediate reaction is, ‘That sounds
horrible,’ ” says Raiany Romanni, a 29-year-old bioethicist
exploring the stories we tell ourselves about death and
meaning. She says she sees acceptance of death not as a
natural part of the grieving process but as naiveté. “I spend
my professional life thinking that death has no purpose,”
Romanni says. “That can be really harmful on a personal
level. But if we keep telling ourselves comforting stories,
it could be infinitely more harmful.”
In the meantime, some of the most hardcore Radicals
are backing the old libertarian play of colonization—
trying to move to one place en masse and make their
ideology a matter of policy. They gave it a dry run for
two months this summer at Zuzalu, a Burning Man-esque
temporary city in Montenegro. There, on the edge of the
Mediterranean, Ethereum’s Buterin gathered hundreds of
longevity true believers, crypto founders and AI researchers to discuss the practical realities of living forever. What
political structures would you need? How could you build
regulation-light “innovation zones” to pursue experimental treatments? If everyone started living dramatically
longer, how quickly would populations grow or (maybe)
shrink? Between cold plunges and sauna sweats, two
venture capitalists unveiled their plans for a movement
called Vitalism, which they said would coalesce around
the belief that “death is humanity’s core problem” and
that the species should do what it takes to “reach freedom from aging as soon as possible.”
Depending on your views, the rhetoric is either
inspiring or ridiculous. But in Silicon Valley, where
wealth and power are concentrated in the hands of a
small crowd of billionaires, winning over a few people
can sometimes be enough.
THE RADICALS
Where accepting your death is a
fallacy meant to protect you from
“the tragedy of wanting something
you can’t have”
mostly took photos and videos for themselves—and
for the benefit of their shared Instagram account. Say
Forever! co-founder Mikhail Batin, wearing a feathered
mask and a pentagram-emblazoned robe, said he was
betting on displays like these to grab the attention of artists, who in turn could have more mainstream persuasive
power than the average peer-reviewed paper.
In the meantime, the various longevity factions are
making progress in their own ways. In November, the
FDA approved part of Loyal’s application for a drug
meant to lengthen big dogs’ lives by blocking a specific
type of growth hormone once they’ve reached their
full size. The drug could be available for your Great
Dane or mastiff in 2026. Meanwhile, particularly wellcapitalized Wellness Obsessives are scoping out longevity
tourism, flying overseas to get experimental treatments.
Diamandis is charging $70,000 for a five-day tour of various private longevity clinics. And a group that includes
some Zuzalu organizers is planning to create a pop-up
city this winter on the Caribbean island of Roatán.
Some Radicals are also hoping a mega-funder such
as Elon Musk will sponsor their dreams over the next
decades. Musk, for his part, recently said he thinks
extreme longevity would cause the “asphyxiation of society.” Elsewhere, he said, “I can’t think of a worse curse
than living forever.” Says Linden, the philosopher: “We’re
all hoping for Elon Musk, obviously, to wake up.” <BW>
THE LOONGEVITY ISSUE
M
ore traditional researchers are very
aware that two-month bacchanals and
multimillion-dollar treatment regimens
can make their field sound like a distraction for the rich. Loyal CEO Halioua,
who researched the economics of gene
therapy at Oxford University, says the broader industry is “sketchy,” and people who overhype the benefits
of unproven treatments or talk about immortality are
causing a “massive reputational issue.” To her, people
like Johnson and Buterin help relegate longevity science to the fringes.
Some of the field’s leaders have been discredited in
other ways, too, she says. In 2021 she and investor Laura
Deming both alleged that de Grey, the onetime face of
longevity, had sexually harassed them. Deming, who
began working in a longevity research lab at 12, wrote
that when she was 17 and 18, she received emails from
de Grey, a trusted mentor, calling her “hotter than hell”
and lamenting that because of her age they couldn’t discuss his “adventurous love life.” Halioua alleged that at
a fundraising dinner for de Grey’s foundation, which
funded some of her research, he “funneled me alcohol
and hit on me the entire night” and said that “as a ‘glorious woman’ I had a responsibility to have sex with the
donors in attendance so they would give money to him.”
The foundation’s investigation into de Grey’s conduct
upheld both women’s principal claims and also found
that he’d interfered with the investigation. He was fired
and has now started another longevity organization.
Halioua says it’s disappointing that de Grey is still appearing at some longevity conferences, but she feels satisfied
that a quick Google search can spare others from what
she and Deming experienced. In an interview, de Grey
dismisses the allegations as overreactions to anodyne
comments. He calls his firing “that whole shit show” and
says it was a cover for his board to wrest power from him.
De Grey’s reputation has taken a hit, but the “Say
Forever!” volunteers were still thrilled when he showed
up at a recent gathering of theirs in San Francisco. It was
the Saturday before Halloween, and a dozen Immortalists
had costumed themselves as vampires and shamans,
wearing bird masks and faux-bearskin capes and carrying plastic skulls and rain sticks. They paraded along the
city’s Embarcadero waterfront, dancing and miming
along to a heavy-metal-esque song with lyrics by Gries,
the longevity investor. “I’m begging, wake up!” the singer
growled in the recording. “Save our loved ones from brutal decline / Give the finger to old Father Time.”
A few curious strangers approached, but the attendees
TEACHIN
18
DL
O
G
RA
TS
NEW TRICKS
Around the world, laboratories are learning how human aging works—
by cultivating elder rodents
By Cara Giaimo Photographs by Justin J. Wee
CREDITS CREDITS CREDITS
THE LOOONGEVITY ISSUE
20
MILD-MANNERED EVERYMICE
The world is full of creatures that age in ways humans
might consider aspirational, including bowhead whales
that enjoy a cancer-free life that can span two centuries
and jellyfish that respond to stress by becoming polyps
again. Researchers look into their methods to learn more
about the evolutionary tweaks that allow for good health
and long life spans.
Mice are not like that; they’re like us. “Their similarity to humans is profound,” Rosenthal says. In general,
mice are good models for biomedical studies because of
all they share with people: the same organs and physiological systems, undergirded by an almost identical set
of genes. “We don’t have big ears and tails, and no fur,”
she says, but “the inside is totally identical.”
Since at least the 1920s, researchers hoping to understand how and why aging occurs have watched ordinary
lab mice go through it. Early on, the work was largely
descriptive, says Richard Miller, a professor of pathology
at the University of Michigan. “You’d get lots of papers
saying the skin changes when the mouse gets old, and
[the reflexes get] slower, and the heart changes and the
bones change.”
In 1935 a group of researchers led by nutritionist and
gerontologist Clive McCay made a breakthrough. They
put a group of rats on a nutritious but calorie-restricted
diet and found that they lived about 33% longer than average. This was the first demonstration “that aging could be
slowed down,” Miller says. According to Roger McDonald
and Jon Ramsey, writing in the Journal of Nutrition, it also
established “a fundamental prerequisite for valid longevity studies”—that animals “must be given the opportunity
to achieve old age.”
After that breakthrough came a small flurry of studies,
establishing that one or another drug helped to extend
life span in a group of mice. But, Miller says, the high
cost of more systematic investigations—as well as the
idea, once pervasive, that aging is too complicated to
slow down—meant these were largely one-offs until 2002,
ET THE LAB RO
E
DE
M
NT
S
DWARF MICE LACK GROWTH
HORMONE, WHICH MAKES
THEM SMALLER AND EXTENDS
THEIR LIFE
SPRAGUE-DAWLEY RATS HAVE
BEEN PART OF MANY AGING
RESEARCH MILESTONES
HET3 LAB MICE HELP
RESEARCHERS UNDERSTAND
HOW AGING INTERVENTIONS
AFFECT LIFE SPAN ACROSS
DIVERSE POPULATIONS
COSTUMER: CAMMI UPTON; PROP STYLIST: GRAYSON FISHER. THIS PAGE: PHOTO ILLUSTRATIONS BY JUSTIN METZ. SOURCE PHOTOS: SHUTTERSTOCK (3)
LAB RATS
DEEECEMBER 2023
E
ach day technicians at the Jackson Laboratory
in Bar Harbor, Maine, check on special groups
of mice in their care. The mice are all more than
600 days old, roughly 60 in human years; some
are much older. A few may need help reaching their
water dispensers, but many are how humans hope to
be as we age: “curious, energetic, unbelievably active,”
says Nadia Rosenthal, the lab’s scientific director. “It
takes them a little longer to run from one side of the
cage to the other,” but often “that’s the only difference.”
In medical research, lab mice and rats die for us in
great numbers. Sacrificed during or after experiments,
they leave us with information that, over the years, has
helped us understand diseases, develop medicines and
map the functions of particular genes. But some agingfocused research projects require something else from
these animals: that they stay alive, and healthy, for as
long as possible.
So in labs from North Dakota to Mumbai, select
rodents grow old under heavy scrutiny. Tucked away
from the world to avoid pathogens and other confounding variables, sleeping in piles and doing flexedarm hangs, and soldiering on as their cage mates
die, they’re helping to illuminate certain mysteries
of aging and test the efficacy of life-extension methods that may eventually be used for humans.
They are rarely sung heroes in our quest to understand, and perhaps soften, the ravages of time.
LAB RATS
DEEECEMBER 2023
21
THE LOOONGEVITY ISSUE
when he and others began an ongoing project called the
Interventions Testing Program (ITP).
For this study, which is funded by the National Institute
on Aging, three labs in three states—at Maine’s Jackson
Lab, the University of Michigan and the University of
Texas Health Science Center in San Antonio—collectively
raise hundreds of mice each year, in highly controlled
conditions. A subset of these mice are given drugs that
seem promising for life span extension and are supported
to live for as long as they can.
Participants in the ITP belong to a lab mouse stock
called UM-HET3, or HET3 for short. Many popular lab
mouse types are inbred and thus genetically identical.
Studying a whole group of these mice is “like studying
one person”—of limited utility when trying to find interventions that might help the whole human population,
says Rosenthal, a co-principal investigator in the ITP.
While wild mice are naturally diverse, they’re difficult
to work with: Lab veterinarians handling them sometimes wear protective chain-mail sleeves.
HET3s, who as pups range from brown to black in
color before settling on a grayish shade called agouti,
were bred to be the best of both worlds: robust yet
mild-mannered Everymice. All HET3 mice share the same
grandparents, and thus half their genes, but “a random
half,” Miller says, making each cohort genetically diverse
enough to be “a valuable model for people.”
With each population’s genes reasonably jumbled, the
ITP researchers, veterinarians and lab techs work hard to
make sure almost everything else about the life of each
mouse is exactly the same for each cohort—enclosure to
enclosure, lab to lab and year to year. This level of control
allows them to test the efficacy of specific drugs and drug
combinations. If a particular intervention extends mouse
life span in many of these genetically diverse mice, and at
all three sites, “you know you’ve really got something,”
says Peter Reifsnyder, manager of the Harrison Lab, which
supervises ITP studies done at the Jackson Laboratory.
Not everything can be successfully controlled for. ITP
researchers are unsure why male mice that participate
in the study in Michigan always live a bit longer than
those in Maine and Texas, or why both male and female
mice in Michigan weigh slightly less than their cross-state
counterparts despite an identical diet. Miller speculates
that there may be differences between the sites that matter to mice but are imperceptible to us—“maybe there’s
a smell at Michigan that they like,” he says.
Over the years, the ITP has surfaced several promising
life-span-increasing interventions. The most successful,
mousewise, is a combination of the immunosuppressive drug rapamycin and the glucose regulator acarbose, which allowed mice in the ITP to live an average
of 29% longer. Other stakeholders are now investigating
these and other successful drugs further, in mice, different study animals or occasionally themselves, Miller says.
The Jackson Lab runs numerous mouse aging studies and sells pre-aged mice to other research groups. (A
single 90-week-old HET3 mouse costs almost $600.) The
mice are visited every day, and aged ones get considerations related to their status, says head veterinarian Linda
Waterman: “Can they reach their food and water readily?
Do they have soft bedding?” In geneticist Gary Churchill’s
lab, technicians keep “a whole list of old-fashioned female
names” to give mice when they turn 4, he says, a tradition that dates to around 2016, when two particularly longlived mice, from a different study of genetically diverse
mice, were christened Grace and Blanche.
This careful attention extends up to the very end
of a mouse’s life. When mice in the ITP do eventually
die, they’re put in fixative as quickly as possible so the
researchers can study their tissues. If it seems a mouse
will die in the next day or two, they may be humanely
euthanized to prevent suffering and ensure their tissues
are well-preserved.
The need to balance gathering accurate life span data
with these concerns has led Reifsnyder to brainstorm
potential ways to keep track of his charges’ body temperature, which dips before death. So far, “we haven’t
come up with a best way of knowing exactly when a
mouse is going to die,” he says, though it’s something he
puts a lot of thought into.
Without a system, experience is key: “Most of the people who work at [the Jackson Laboratory] have a kind of
a sense for when a mouse is experiencing well-being versus not,” says Rosenthal, who, she says, works with one
LAB RATS
DEEECEMBER 2023
22
technician who’s so attuned to her mice that she can
predict their deaths. “It’s so important to spend a lot of time
with your model organism, so that you really get to know.”
THE LOOONGEVITY ISSUE
ZEN AND THE ART OF
PHYSIOLOGICAL MAINTENANCE
The world’s longest-living lab mice are a special class
of rodents known as dwarf mice. These tiny titans
have mutations that block the production or actions of
growth hormone, thanks to natural gene misprints or
genetic engineering.
Each dwarf mouse is about as big as an unshelled walnut, with a round face, snub nose and tiny feet. “The
cutest things ever,” says Holly Brown-Borg, a biogerontologist at the University of North Dakota who works with a
particular strain called Ames dwarf mice. And they’re very
chill: Andrzej Bartke, director of geriatric medicine at the
Southern Illinois University School of Medicine and a pioneer in the use of dwarf mice to study aging, has posed for
headshots with one perched on his shoulder like a parrot.
For reasons experts are still untangling, these Zen minimice have an average life span that can stretch over 60%
longer than that of their traditional relatives, including
their siblings. (Their mutations are recessive, so a litter
of mice may contain both normal-size mice and dwarf
mutants.) Many dwarf mice live longer than four years,
making them the equivalent of centenarian humans:
rodent sages, each in the body of “a big baby mouse,”
Bartke says.
Because lab mice are so rarely given the opportunity to
age beyond their perceived usefulness, the dwarf mouse’s
penchant for extralong life wasn’t discovered until the mid1990s. Even then it was something of an accident, BrownBorg says. As postdoctoral students in Bartke’s group, she
and her husband, Kurt Borg, were looking for mice of a
certain age for an immune system study when they realized that the lab’s spare dwarf mice were often older than
the regular-size ones. This came after other work, by the
geneticist Thomas Wagner, showed that mice with extra
growth hormone had unusually short life spans. The group
wondered whether the opposite was also true.
When Borg and Brown-Borg set aside some dwarf mice
to see how far they could take things, the longest-lived
made it past four years—long enough for the couple to
finish their postdocs and get jobs. A few years later, in
2003, a genetically engineered dwarf mouse in Bartke’s
lab lived to 4 years, 11 months and 21 days—roughly 180
in human years—winning the Methuselah Mouse Prize,
an award once given to long-lived mice, and setting a lab
mouse life span record that still hasn’t been broken. (This
mouse was also “kind of forgotten—left over from some
study,” Bartke says.)
Since these discoveries, researchers have been looking into the extent of the dwarf mouse’s special powers.
“If we look for mechanisms related to health, these animals are probably teaching us many things,” says Bartke.
They’ve found the little guys are better than normal mice
at handling oxidative stress, a buildup of reactive molecules that can damage tissues. They have “exquisitely
good regulation of blood sugar,” he says. Put on high-fat
A RAT CROSSES THE BOUNDARY
Other researchers prefer to test life span extension
possibilities in rats—also well-characterized lab animals that share genes and physiology with humans. The
world’s oldest known lab rat died on March 3 of this year,
in the animal facility of the Shobhaben Pratapbhai Patel
School of Pharmacy and Technology in Mumbai. Her
name was Sima, and she was a Sprague-Dawley rat, a
snowy-furred, rosy-eyed albino strain. Three days before
she passed away, she had turned 4, a milestone her caretakers celebrated with birthday cake.
Sima was the last of her cohort, a group of 16 SpragueDawley rats. She and the others had been procured at
age 2 by Yuvan Research Inc., an anti-aging startup in
Mountain View, California. Every two or three months,
Sima and seven of her colleagues received injections of
E5, a proprietary plasma mixture the company developed that’s made from the blood of young pigs. The other
eight, the control group, got saline placebos.
According to data from the company, whether these
rats were given E5 determined the course and length
of their unusual retirement. (Although this data hasn’t
yet been peer-reviewed or made public, another study
with similar results was published earlier this year in
GeroScience.) Compared with the control group, Sima
and the rest of the experimental group had less inflammation, lower triglycerides and more glutathione, a liver
product that prevents cell damage.
In data from the GeroScience study, rats on E5 solved
and remembered mazes more effectively than those
stuck with their own blood. In the unpublished study,
LAB RATS
DEEECEMBER 2023
diets, they avoid fatty liver disease, and when mice bred
to develop Alzheimer’s-like conditions are crossed with
dwarf mice, their descendants are slower to experience
the hallmarks of that disease.
“There’s something about their metabolism physiology
that helps to slow or prevent some of these age-related diseases,” says Brown-Borg. “They not only live longer, but
they live healthier.” Humans with similar genetic growth
hormone deficiencies don’t seem to have unusually long
life spans. So researchers focus on some of these other
effects, trying to trace their relation to health and life.
Even during behavioral tests, dwarfs aren’t like other
mice, Brown-Borg says. They amble through mazes
and build nests under their running wheels. Dropped
in a warm water bath, where normal-size mice furiously paddle, dwarfs “spread their legs out and float.”
Although this attitude is harder to directly connect to
their long life span, it does seem to contain a lesson.
extend life span, or digging into the traits that tend to
accompany long life, they operate with the assumption
that aging is programmed into mammalian cells, with certain forms of degradation set to begin right after puberty.
They try to hack that process in an older animal by sending in signaling molecules from younger bodies—this can
make cells “closer to the donor’s age,” Sanghavi says.
Scientists have been making rats swap blood since
at least 1864, when a French physiologist named Paul
Bert joined the circulatory systems of two albino rats
through their flanks, a technique now called parabiosis.
Over the years, researchers built on this idea, eventually stitching together rats of different ages and finding
that young blood increased the old rats’ life spans, an
idea now perhaps better known from conspiracy theories
and the unusual behavior of tech mogul Bryan Johnson.
Yuvan Research originally sought to clean up young
rat blood and transfer it into elderly rats, Sanghavi says,
but they couldn’t find an easy way to do it. Instead,
Sanghavi and his co-founder, the geneticist Harold
Katcher, decided to create an injectable: “something that
was in small doses but could be very powerful,” Sanghavi
says. Switching to pig blood meant they could also see if
their driving principle would work across species.
When Sima entered the study, she was known as
Rat T6. Like Grace and Blanche before her, she received
a name when she began outperforming the others in
her cohort. In Sanskrit, Sima means “barrier” or “border,” which Sanghavi says references the natural limits of
aging. “I could see that she was going to cross,” he says.
Life span studies, like those done with Sima and other
record-setters, are just one type of aging research. Now
that the extent of the unusual life span of dwarf mice is
well-established, most of the studies involving them focus
on other things. (In her lab, Brown-Borg always makes sure
a few live out their natural extralong life, “just to make sure
that it’s still happening,” she says.) Other investigations of
the aging process may instead look into how interventions
early in life affect aging rates, or compare different mice
of the same age to see, for instance, how their genes influence how they get old. And in many cases, rodents make
up just one step in a long testing process: Buoyed by their
success with rats, Yuvan Research is moving on to beagles.
But where it’s possible and useful, mice, rats and
those who care for them continue to chase that border.
“For scientists interested in aging, end-of-life is just as
important as beginning of life,” Rosenthal says. So in
places like the Jackson Lab, where the infrastructure
allows them to achieve economies of scale, “we can do
big experiments with hundreds of mice and just let them
live,” she says. “We can keep them in the cages for long
periods of time, for years, and just wait for them to get
older, and watch.” <BW>
23
THE LOOONGEVITY ISSUE
they gripped a bar for longer, showing almost as much
Aged mice get considerations
strength as young rats. Juiced up with the proprietary
pig plasma, “these rats become younger, livelier,” says
related to their status: “Can they
Akshay Sanghavi, the company’s chief executive officer.
reach their food and water readily? “We are able to reverse the biological age.”
Yuvan Research takes a different approach to antiDo they have soft bedding?”
aging. Instead of testing many compounds that might
CREDITS CREDITS CREDITS
Retro Biosciences is experimenting with ways to make
our last 10 years better. Here are its best ideas
By Ashlee Vance Photograph by Samantha Casolari
PLAYING THE
L
ON
GA
G
25
ME
THE LOOOONGEVITY ISSUE
J
oe Betts-LaCroix didn’t have time to wait for
architects, construction workers or really any
of the normal things that go into building a new
office, let alone a new laboratory. It was May 2021,
and he wanted to do experiments … lots of them … right
away. And so he and a small team of people took over
an abandoned retail building in Redwood City, California,
and filled it with shipping containers, which they’d soon
fill with mice. They built the heating and air conditioning
system for their lab pods by hand and did the same with
the air-filtration system and their precisely tuned mouse
vivarium. At the end of two months, Betts-LaCroix’s team
had its first experiments up and running.
“I was told by a nearby developer that’s been building
a similar-sized lab for more than a year that they’re going
to spend $15 million on it,” Betts-LaCroix says. “I probably
spent, I don’t know, $200,000. I’d just rather figure out
how to do it and do it in a way that works.”
The company Betts-LaCroix started, alongside
the scientists Matt Buckley and Sheng Ding, is
called Retro Biosciences Inc. and has a pitch
that’s as ambitious as Silicon Valley gets. It
wants to give every human 10 additional years
of healthy, vigorous life. To pull this off, and pull
it off quickly, Retro has eschewed a number of
biotechnology startup traditions. Most notably,
instead of chasing a single super-promising compound or treatment, it’s decided to pursue five
tracks of research at the same time. It’s a highrisk, costly strategy made possible only by the
company’s unusual backing. Retro has raised
$180 million from one investor—Sam Altman,
OpenAI Inc.’s co-founder and recently ousted
and de-ousted chief executive officer.
The customs of the biotech field dictate more
pragmatism and polish than with other tech startups. In
most cases, companies charge after what they believe
might be a singular breakthrough, and the end goal, after
toiling for years and years and performing a costly clinical
trial, is often to sell whatever results to a pharmaceutical
or medical device giant. Things such as building handcrafted container labs and hopping from one promising
lead to the next are simply not done.
Once upon a time, Altman and Betts-LaCroix had, in
fact, discussed starting a smaller longevity-technologyfocused company around a single therapy, but the more
they talked, the more they became excited by other
things, too. “Usually in this field you get to pick one idea
and spend nine years on it, and then, at the end, maybe it
works and maybe it doesn’t,” Betts-LaCroix says. “Sam was
willing to do something different and throw lots of money
at a bunch of things in parallel.” Betts-LaCroix describes
Altman’s support as “lucky,” “freaking awesome” and
PHOTOGRAPHS BY JUSTIN MAXON FOR BLOOMBERG BUSINESSWEEK
MICE IN
INDIVIDUALLY
VENTILATED CAGES;
RETRO CO-FOUNDER
BUCKLEY
B
etts-LaCroix, who’s 61, can sometimes be
found pacing around the Retro offices with
a 22-pound sphere of tungsten in hand. It’s
about the size of an orange and awkward to
support. He seems to take some pleasure in
passing it to guests and watching to see if they’re up for
the challenge or if their wrists and elbows will immediately buckle as the ball heads toward the ground. In
the latter case, Betts-LaCroix will comment on tungsten’s high density (19.25 g/cm³) and periodic table naming origins (W, from the ore, wolframite), while his guest
BETTS-LACROIX
10 MORE YEARS?
DEEEECEMBER 2023
“cool,” which is what anyone given $180 million to pursue
their hopes and dreams should say.
Retro has operated in secrecy for most of its two-year
existence, and this marks the first time the company has
talked about its work in detail and opened its office and
laboratories for perusal. The company of about 50 people
has small teams shooting for breakthroughs in autophagy
(the removal of damaged cells), the rejuvenation of blood
plasma and three research programs tied to what the
biotech industry calls partial cell reprogramming. Cell
reprogramming is a process, proven out in numerous
animal experiments, in which the cells of an older creature can be treated with a combination of proteins or
molecules and turned into much younger cells. Based on
Nobel Prize-winning science, it’s something Retro and a
handful of other startups consider the most promising
longevity technology to yet appear.
Silicon Valley, more than anywhere else, has for
decades been hoping not only to retard aging but also to
find an actual “cure” for death. This goal has made the
region and its technophiles the butt of many jokes and the
target of criticism. Betts-LaCroix, well aware of the history
and the teasing, has tried to tamp down some of the most
extreme longevity rhetoric. “People don’t want to die,” he
says. “They will latch onto something if given hope, which
is in some ways the force that I’m fighting against. The science of this realm is not the cure to your existential crisis
or your desire to avoid death altogether. There are lots of
things that are going to kill you. But this type of technology could extend healthy human lifestyles by years, and
it’s an incredible gift to humanity. It’s worth working on.”
Retro and its peers really do think this time is different. Many researchers in the field contend that the science behind cell reprogramming, in particular, has been
solved and that therapies are now an engineering problem. They see full-on age reversal as not only achievable
but also perhaps imminent. That’s why the race is on—and
why you might want to build a lab in a hurry.
blushes and makes internal pledges to go to the gym
more. (Not that this happened to me.)
The detailed talk about tungsten or the physics
of HVAC systems reflects Betts-LaCroix’s autodidact
nature, shaped and encouraged during an unconventional childhood in Oregon. He grew up in the heart
of the 1960s counterculture movement with parents
who largely let their son do as he pleased and explore
what he wanted to explore. When, as a 7-year-old,
Betts-LaCroix took apart the family’s sewing machine
and refrigerator, that was considered just fine. And if he
ran late to school, his parents would send a note asking
for him to be excused on account of alien abduction.
“My father taught me you can redesign anything from
first principles,” Betts-LaCroix says. “I was in a subculture where we considered ourselves to be redefining
society. We were starting over from a blank slate and
could make our own rules.”
Outside of physics and math courses, Betts-LaCroix
hated high school and rarely attended class. He graduated with a D average, then spent the next six years living
in a shared house with “musicians, artists and weirdos.”
Betts-LaCroix set up an electronics lab in the basement
and performed a constant stream of electromechanical
experiments. He covered his expenses by doing electronics, hardware and software work for local businesses and
occupied the rest of his time by consuming huge quantities of books.
Eventually a girlfriend of Betts-LaCroix’s got into
Harvard College, and he decided to follow her. He
spent a semester at a local college, buckled down,
got straight A’s and submitted what he describes
27
10 MORE YEARS?
DEEEECEMBER 2023
ONE OF RETRO’S
LIQUID-HANDLING
ROBOTS HELPS
PERFORM RESEARCH
AUTONOMOUSLY
THE LOOOOOOOONGEVITY ISSUE
28
as an unusual transfer application that impressed
the admissions office. Once at Harvard, Betts-LaCroix
found that his relationship with school and academics
changed. “It was like, ‘My God. This is a secret treasure
trove,’ ” he says. “I could hang out with these brilliant
professors and talk to them and learn from them. I wondered where this had been all my life.”
At Harvard he obtained an undergraduate degree
in environmental geoscience while doing biophysics
research at the California Institute of Technology in
his spare time. Later he built robotics systems at the
Massachusetts Institute of Technology, all the while publishing a stream of papers across these fields in scientific
journals. After moving to Silicon Valley, he co-founded
OQO Inc. in 2000, which was a much celebrated though
unsuccessful maker of tiny personal computers, and
then worked at the much celebrated though unsuccessful gene-sequencing startup Halcyon Molecular Inc. In
more recent years he’s been a prolific angel investor in
startups and a well-known figure in biohacking, longevity and quantified-self circles.
Beyond OQO and Halcyon he spent time working at
a couple of other technology companies, in the venture capital realm and as the chief technology officer of
Vium Inc., which tried to add automation and precision
to the field of animal testing. In the background, however, he hosted and attended longevity technology salons
and events. These activities were more of a hobby, a side
passion. That is, until a series of scientific breakthroughs
proved too strong a call.
I
n 2006 the Japanese surgeon-turned-researcher
Shinya Yamanaka made a dazzling discovery.
He took skin cells from an older mouse and
turned them into stem cells (specifically, what
are known as pluripotent stem cells). In other
words, he transformed a group of cells that the
body had configured to perform specific functions and
rewired them back to their original, blank state.
Researchers had long theorized that such a feat might
be possible but assumed the techniques needed to perform the reversal would be complicated and require years,
perhaps decades, of experimentation. Yamanaka and his
team stumbled upon a combination of four transcription factors, proteins that ferry instructions to DNA, that
talked the older cells into activating genes that are usually
turned on and buzzing only in the earliest moments of life.
Yamanaka received the Nobel Prize six years after publishing his paper on the science, and so-called Yamanaka factors are now famous throughout the biotech world.
We all start as blank canvases. Embryos initially have
undefined stem cells that, as they divide and develop into
fetuses, take on specialized roles as liver cells, neurons,
heart muscle tissue and so on. It’s an amazing process in
that all the stem cells share the same DNA, but over time
they start to emphasize different parts of their genetic
code and form unique identities. Observing how these
transformations take place has been of major interest to
scientists trying to discover the root cause of diseases
and degeneration. Before Yamanaka’s breakthrough,
stem cells had to be harvested from embryos, and this
process carried with it ethical controversies and biological limitations. Post-Yamanaka, researchers can more or
less create stem cells at will.
Yamanaka’s finding was exciting enough that it paved
the way for a new era in stem cell research. But it was
work led by scientist Alex Ocampo and his colleagues
“We want to build the best way
to test as many transcription factor
combinations as possible and
also to predict which ones are
most worth going after”
DEEEECEMBER 2023
sometimes have their cells
reprogrammed and then
start growing tumors known
as teratomas all over their
bodies. This, of course, adds
major caution to any human
experimentation. “There’s
thinking that you can inject
a virus that will go into
someone’s tissues, put the
genes for these transcription
factors into the cells and
express them for a while in
hopefully a very controlled
way,” Betts-LaCroix says.
“You have to stop before you
go too far and make a pluripotent stem cell, because it
LIQUID NITROGEN
will start trying to grow an TANKS STORE
entire person right there CELLS FOR LONG
PERIODS
and form the tumors.”
Ocampo now has a lab in Switzerland that focuses
on partial cell reprogramming. He remains encouraged
by the technology, though with some caveats when it
comes to the idea of developing safe longevity therapies for humans. The genes linked to partial cell reprogramming are tied to higher incidences of cancer when
they’re expressed at high levels. In addition, the means
of delivering potential therapies to a wide range of cell
types remain limited. “You can reach places like the
liver easily, but the brain and heart are more difficult,”
Ocampo says.
It could take many years for these startups to create
safe, approved treatments. Ocampo doubts a therapy
delivered straight into the body based on the Yamanaka
factors will arrive this decade. “However, I think that
other techniques and treatments using alternative factors
or small molecules could be possible,” he says. “Overall,
reprogramming is the technology with the strongest
potential, and I don’t think anything else in the longevity field comes close.”
29
R
etro’s headquarters are split into three
main areas. There are offices that have
been decorated true to Betts-LaCroix’s
counterculture vibes. One small room,
for instance, has jellyfish wallpaper on one
wall and some sort of cotton-ball material
on another that’s meant to evoke a cloud.
The bathrooms have LED lights that project star patterns and different colors. A second, mid-building section is full of lab and DNA-sequencing equipment, much
of which Betts-LaCroix got on the cheap from Curative,
a onetime Covid-19 testing highflier that’s morphed into
a health insurance company.
Most of the square footage is taken up by the mouse
and tissue testing facilities. In its earliest days, Retro had
two vivarium shipping containers full of mice and one
container for conducting cleanroom-style tests. Now
it has more than a dozen containers and adds new
THE LOOOONGEVITY ISSUE
then at the Salk Institute that redirected some of the
attention around Yamanaka factors toward the longevity field. Ocampo bred mice with the factors inserted into
their genes and developed a means for turning the reprogramming mechanisms on for a couple of days at a time.
When this process was done just right, the mice showed
broad rejuvenation among their organs and ultimately
lived 30% longer than unmodified peers. A paper based
on this research appeared in 2016 and soon led to a slew
of startups trying to further the science and turn it into
the basis of longevity therapies.
Retro is one of a handful of startups that have based
much of their research and business prospects around
these advances in cell reprogramming. NewLimit Inc., a
company co-founded by Coinbase Global Inc. CEO Brian
Armstrong, has set out to do a massive survey of thousands
of transcription factors in search of the best combination
of proteins for stunting or reversing aging. This project
requires the company to compare and contrast blood cells
gathered from young and old donors and to run a constant
stream of DNA-sequencing tests and computational analysis as the cells are altered by various transcription factor
recipes. “We want to build the best way to test as many
transcription factor combinations as possible and also to
predict which ones are most worth going after,” says Jacob
Kimmel, a co-founder and head of research at NewLimit.
Investors—including the venture capital firms
Dimension, Founders Fund and Kleiner Perkins and individuals such as former Google CEO Eric Schmidt, tech
investor Elad Gil and Y Combinator CEO Garry Tan—have
agreed to put $40 million into NewLimit, and the company’s founders have pledged $110 million more. That’s
a significant amount of funding, but it’s well behind the
$3 billion that Jeff Bezos, investor Yuri Milner and others
are reported to have poured into Altos Labs Inc., another
Silicon Valley cell-reprogramming startup. Altos has
recruited some of the top scientists from academic labs
around the world, trying to turbocharge their research
by giving them more funding and resources. The company declined to comment.
While the particular goals of these businesses vary,
their overall mission is shared. They’re not looking to
revert skin or liver or brain cells all the way back to
their blank, stem cell state. Rather, they’re trying to find
ways to regress damaged or decaying cells to a healthier, younger condition. Many promising experiments
have been done with animals and tissue samples where
exactly this process has taken place. Sometimes, however, the experiments run amok. Mice, for example,
TEKAY SUBJET MATTER
SHINDYAPINA;TRAPP
THE LOOOONGEVITY ISSUE
30
ones as the operation expands. All the containers are
interconnected via lab-grade HVAC and air-filtration
systems that Betts-LaCroix and his team built from scratch.
Many of the thousands of mice are immunocompromised as a result of the experiments taking place within
their cells. So researchers must don protective gear and
go through an air lock before entering the vivarium. “One
germ can ruin the mice’s whole day,” Betts-LaCroix says.
The mice live in shoebox-size plastic containers full of little blocks of wood they can chew on and other material
they can use to make nests. Retro has tried to be very precise with lighting and temperature for the mice by placing
sensors and control systems on each container instead of
treating the conditions of the room as a whole, as is typical at other research centers. “Nobody tracks that some of
the mice in their experiment were near the top of a rack
of cages versus near the bottom, where they might get less
light,” Betts-LaCroix says. “And then they wonder why they
can’t replicate the results of their experiment. It’s a huge
problem. One of my life agendas is being on this warpath
to improve animal experiments. These mice are making
a sacrifice, and we should make it count.”
Retro has a variety of cell-reprogramming experiments going, including studies in mice and some with
human tissue gathered from patients suffering from cancer. On the cancer front, one team has been working to
reprogram T cells to better attack solid tumors. It’s common for T cells to exhaust themselves and shut down
as they try to combat the rapid growth of cancer cells.
Although it’s early
days, Retro says it
may have found a way
to flip some switches
in the T cells to keep
them fighting. It’s
been running experiments on tumor samples removed from
sick individuals and pounding them with its reformatted T cells. Another project centers on reprogramming
liver cells to return them to a younger state.
Retro’s most promising reprogramming effort may be
the one run by Anastasia Shindyapina, a staff scientist at
the company. She heads a program to rewire humans’
immune systems. Shindyapina hails from Russia, which
has a long-held cultural fascination with longevity technology, and met Betts-LaCroix at a Silicon Valley biotech
gathering where he persuaded her to abandon academic
work in favor of chasing Retro’s varied, high-risk bets.
“It was in the early, early days of Retro, and no one
knew if this would turn out good or bad,” she says.
A rejuvenated immune system could have some of the
broadest possible longevity effects, as numerous types
of cells throughout the body would be able to block and
hunt down disease better and repair the body more
quickly, the way we do in the prime of our youth. Over
the past year, Shindyapina says, her team has produced
ever more encouraging results. “When your immune
system is screwed up, it affects every tissue,” she says.
“You have to target the immune system first, and it will
give rise to everything else.”
The human body has more than 1,500 transcription factors, which can be combined in an astronomical number of ways. Picking which factors to focus on
requires machine-learning algorithms that can parse the
data and hunt for patterns. The labs at Retro, NewLimit
and elsewhere are full of DNA analysis machines made
by 10x Genomics Inc. The company has pioneered
10 MORE YEARS?
DEEEECEMBER 2023
gene- sequencing techniques that let scientists study
changes taking place within individual cells. “It allows
us to understand biology with far greater resolution,”
says Buckley, one of the Retro co-founders. “If you can
rejuvenate a single cell, maybe you can rejuvenate some
tissue and then maybe an organ and then maybe the
entire organism.”
Buckley and Alex Trapp, a staff scientist at Retro, have
been at the forefront of this computational biology revolution for years. Their work stretches across not only the
cell reprogramming but also areas such as autophagy and
blood plasma research. In the autophagy arena, Retro
has been trying to develop an injection or pill that could
mimic the benefits of caloric restriction, which leads the
body to cleanse itself of old, damaged cells. And
AN ANIMAL
with the blood plasma work, Retro is playing TECHNICIAN CHECKS
off the years of research that show old animals ON A SUBJECT
benefit from being infused with the plasma of
younger animals. Although the studies here have
been encouraging, the actual means of doing the
transfusion is off-putting: In addition to being a
time-consuming process resembling dialysis, it
basically involves the old feeding off the young.
Here again, Retro looks to produce a therapy in
a pill or injection that would trigger the effects
of the plasma exchange without having to actually perform a physical swap.
At every turn, Retro’s future hinges on bets,
crossed fingers and faith that this is the moment
when biology and computers really will unlock
the secrets of how the body works. For encouragement, Trapp points to that miracle of longevity, the naked mole-rat. “They live for 40 years
and never get cancer and never have any agerelated pathologies,” he says. “We can look at
how these other species have evolved over millions of years to do particular things and harvest
those insights.” He also points to the simple idea
that human bodies, without question, know how
to rejuvenate. At conception, embryos combine
and reset old and damaged genes into a healthier, cleaner state. “If this didn’t happen, people
would get continuously older and carry on the
damage from their cells,” Trapp says. “Obviously
the body and evolution have figured out how to
do this. Now we need to figure out how to do it
artificially ourselves.”
The amount of money that Retro, NewLimit
and Altos Labs have raised is both staggering and not. These companies are pursuing
31
THE LOOOOOOOONGEVITY ISSUE
technology that could reshape human life. In a world
where Hollywood will place equal-size financial bets on
several movies in the coming year, it’s actually almost
shocking that more companies haven’t opted to chase
what could be the best business of all time.
The hard truth, of course, is that many, many promising biotech companies have gone bankrupt on their
journey to prove the merits and safety of their products.
Five research areas mean at least five clinical trials, each
requiring a lot of time and money. “Sam will not be able
to fund this all the way,” says Ding, the Retro co-founder
and famed researcher in the cell-reprogramming field.
“Getting to the final products will require more investors
and going public at some point. I’ve seen plenty of very
fancy companies crash and burn along the way. The magical story can only be told for a limited number of years,
frankly, before you see results.”
At the same time, Ding maintains that Retro’s funding
and nimble operations give the company as good a chance
as any to succeed, and he’s as confident as ever that a
solution to aging is right at hand. “Often in scientific
discovery, you can go for years or even centuries looking for the answer to problems,” Ding says. “Here we
know the answer.” <BW>
M
A
R
G
0
YOUR GENES
R
REP
An unproven injection to boost muscle-building proteins
is being tested in Honduras, and it has one very enthusiastic guinea pig
By Ashlee Vance Photograph by Thomas Albdorf
in development; and that Minicircle’s approach will lead
to longevity for all. “Most gene therapies cost more than
$1 million a pop,” he says. “This therapy is made so that
anyone in the world can have access to it.”
But, for now at least, Minicircle’s therapy isn’t for everyone. Some scientists familiar with the company’s work
have criticized its claims and doubt follistatin increases
would result in even minor life span gains. Minicircle has
yet to publish clinical trial data and has been reluctant to
speak about some of its development methods. And, while
its product will be priced lower than typical gene therapies, it still runs about $25,000 per treatment. “These have
no evidence for working, don’t make sense from a scientific perspective and likely will kill someone by inducing
cancer or liver failure,” Christin Glorioso, a physician and
neuroscientist, writes about follistatin and other unregulated gene therapies in her longevity and health newsletter.
While Minicircle works to get its trial data out into the
world, it’s also been hoping to generate buzz among longevity enthusiasts. One way to drum up attention would
be an endorsement from a longevity influencer. But
where in the world would the company find someone
prominent who’s willing to take an unproven gene therapy just for kicks? Who in their right mind would volunteer to head to Honduras and fiddle with their cells,
just because the people running a libertarian technocapitalist free zone said it was chill?
B
ryan Johnson landed in Roatán in September.
Over the course of the previous nine months,
Johnson had risen to fame as the world’s bestknown and most controversial longevity
explorer. He earned this reputation, in part, by
developing a health program known as Project Blueprint,
in which he meticulously manages his diet, exercise regimen, sleep, supplement intake and various rejuvenation
therapies and then publishes detailed medical data documenting the changes taking place in his body. The elevator pitch for all this is that Johnson is spending more
than $2 million a year on his body in a bid to slow or, if
possible, reverse the aging process and test the limits of
current longevity technology.
This has made him a hero to some health enthusiasts,
but to others he’s an example of extreme narcissism,longevity aspirations gone absurd. Johnson has embraced
all sides of his newfound fame; he turned up in Roatán
with a videographer, always by his side, whose job was to
help produce TikTok and Instagram posts about the gene
therapy process. The videos would make for good content, as Johnson crossed into new, more extreme medical
ASHLEE VANCE
INJECTIONS
DEEEEECEMBER 2023
THE LOOOOONGEVITY ISSUE
34
A
bout a million tourists descend upon
Roatán each year. The island, just off the
coast of Honduras, boasts a large barrier
reef ideal for scuba diving and snorkeling,
and it has the beaches, jungles and slow
pace of life prized by cruise ship types.
One group of visitors, however, recently visited Roatán
with a less conventional goal in mind: They’ve opted to
become some of the first genetically enhanced humans.
These medical tourists came to receive a homegrown
gene therapy made by Minicircle Inc., a small US startup.
The therapy, delivered via injection, turbocharges the
body’s production of follistatin, a protein that helps
manage production of other proteins and hormones. The
company’s founders say the therapy can reduce inflammation throughout the body, increase muscle mass and
bone density, extend exercise endurance and improve
hair and skin. It is, according to Minicircle, “the holy
grail of muscle, bone and fat” and one of humanity’s
best hopes for “extreme longevity.”
The therapy hasn’t been approved by the US Food and
Drug Administration, which is in some ways the point
here. Minicircle—backed by the venture capital billionaire Peter Thiel, OpenAI Inc. co-founder Sam Altman and
other technologists—is an experiment on an experiment.
The company is based in Austin but works out of Roatán
because Honduras granted the island considerable regulatory freedom when it comes to technological and scientific ventures. Minicircle more or less just needed to
buy some insurance and get the patients’ acknowledgment that they knew they were heading into the great
unknown. “It’s really about expediency,” says co-founder
Walter Patterson, who’s also the chief scientific officer. “We
are gearing up for a trial in the United States, and we are
going through the FDA. But, keep in mind, it’s prohibitively
expensive in terms of both time and money. We’re here in
Honduras because we can essentially do things quicker.”
Patterson has an easygoing manner, a mild
Appalachian drawl and academic credentials that are
considerably thinner than one might expect from a biotech executive. In 2019 he dropped out of the University
of North Carolina to start Minicircle and soon became
renowned among biohackers. He and his co-founder, Mac
Davis, have also impressed big biotech names, including
George Church, the celebrated Harvard University genetics professor, who’s described them as knowledgeable
and methodical. The follistatin therapy is the first in a
series of products Minicircle plans to roll out, including
therapies for DNA repair and tissue rejuvenation. Both
Davis and Patterson injected themselves with the follistatin product years ago. They’re far from muscle-bound,
but they say their bodies have become thinner and firmer
despite spending little time working out.
Patterson says Minicircle didn’t go to Honduras only
because it’s easier, and the company certainly wasn’t
trying to be reckless or cavalier. He contends that biotech and longevity advances are at hand and that people of sound mind and body should be able to partake
in those advances if they so choose; that innovation in
this field need not cost hundreds of millions of dollars
JOHNSON HAS BLOOD
DRAWN BEFORE THE
MINICIRCLE INJECTION
territory. “We’ve built out the basics of diet, exercise,
sleep and all the stuff we know we should do,” he said
before the trip. “But that’s not going to get me to 200 years
of age. Gene therapies have the promise of doing that.”
You can find photos online of animals that have
been genetically engineered with techniques similar
to Minicircle’s therapy, and the creatures are extraordinary. Cows with extra helpings of muscle-growing
proteins running through their veins look like bovine
Avengers. They bulge so much and from so many places
that it almost appears painful, as if their skin is struggling to contain the rippling tissue.
Minicircle’s therapy is designed to produce a milder
effect. The company packages the biological instructions to increase follistatin production into a plasmid,
which is a small, circular bit of DNA with properties
similar to those of bacteria. The plasmid, whose shape
inspired the Minicircle name, is then injected into
some fat cells, usually near the abdomen. The therapy
doesn’t alter a person’s cellular DNA but does introduce
new genetic instructions into cells, sort of like a program running on top of a computer’s operating system.
Enzymes inside cells see the command to make more
follistatin and get to work.
In this case the follistatin is meant to subdue another
protein—myostatin—which tempers muscle growth.
Studies of mice have shown that damping myostatin production results in much beefier, longer-living rodents. “We
are just adding a protein to the blood that signals the body
to regenerate,” Davis says. “In that sense it’s a general
therapy instead of fixing one specific mutation, as you
might do with someone with an ultra-rare disease. We’re
making enhancements that anybody could benefit from.”
Muscle growth varies with age. In an effort to help us
survive and thrive leading into our prime reproductive
years, the body kicks certain processes into higher gear
to build up muscle and stamina. As we pass through
adolescence and become genetically less useful, the
body shuts down some of these calorically expensive
processes, and muscle growth slows, Patterson says.
“Our bodies are designed to get to sexual maturity, and
then you’re supposed to do something about that and
have kids,” he says. “Nature does not care how long we
make it after that. We kind of got dealt a bad hand.”
The Minicircle injection begins increasing follistatin
production immediately, and it peaks over the course of
two to four months. It’s then meant to keep doing its job
for 18 months to two years. If a patient doesn’t like the reaction they’re having or the results, they can turn off the therapy with an injection of the antibiotic tetracycline. The
Minicircle founders describe this as an instant “kill switch”
and say they’ve both experimented successfully with turning their therapy on and off over the past few years.
For its medical trial, Minicircle picked 44 people
age 23 to 89. They were given the same dosage of the
gene therapy and then tracked for three months. Using
THE LOOOOONGEVITY ISSUE
35
diminished business opportunities as a result of her
relationship with Johnson. Southern sought more than
$1 million in damages and a jury trial. Johnson denied all
the accusations, and an arbitrator recently ruled in his
favor and dismissed the claims while ordering Southern
to pay $584,000 in legal fees that Johnson incurred as a
result of the case. Still, the drama between the two has
been the subject of ongoing media coverage.
E
arly on the morning before his procedure,
Johnson was walking around the grounds of
Las Verandas, a vast resort with white villas,
palm trees and a pair of infinity pools overlooking endless turquoise ocean. Johnson, wearing white
shorts and a black T-shirt with the words “DON’T DIE,”
was filming social media videos in different locations.
“I flew to a secret island to get a gene therapy that
may change the future of the human race!” Johnson said
excitedly to the camera at one spot. He then turned to his
crew and asked if the performance was too over-the-top.
“We want to maybe take inspiration from MrBeast but not
try to be MrBeast,” Johnson’s cameraman advised, referencing the world’s biggest YouTube star.
Las Verandas is one of the choicest properties on
Roatán, and it plays host to wedding parties, tourists and
the like. It also happens to be one of the main hubs of
Próspera, a city-building project that made Johnson’s gene
therapy adventure possible. The backstory is strange:
About a decade ago the Honduras government approved
the creation of a handful of special economic zones that,
while governed by Honduran criminal law, could have
more latitude to create their own economic, political and
civil law systems. The country hoped to give rise to its
own Shenzhen or Dubai, which were established almost
as city-states with singular business philosophies.
Exactly who owns Próspera remains a mystery. Thiel
and Marc Andreessen, another venture capitalist, are
among the backers of the $120 million project, though
it’s unclear if they’re major or minor investors. Erick
Brimen, Próspera’s founder and chief executive officer,
declines to identify his shareholders.
Opinions on Próspera are mixed. Some locals have
welcomed the tech-forward push and the possible jobs it
could create. Others have a deep distrust of the wealthy
nerds turning up, buying a bunch of land, living under
their own laws and paying lower taxes. The current
Honduras president, Xiomara Castro, isn’t a fan and
has been trying in court to undo the laws that made the
developments possible.
“These have no evidence for
working, don’t make sense
from a scientific perspective and
likely will kill someone”
ASHLEE VANCE
INJECTIONS
DEEEEECEMBER 2023
THE LOOOOONGEVITY ISSUE
36
biomarkers that assess the aging process, Minicircle
estimated that the patients lowered their genetic age by
11 years on average. “We also saw improvements in muscle mass, bone density, decreases in body fat and general
feelings of enhanced well-being,” Davis says. The major
side effect for some patients was elevated cholesterol levels. But, again, Minicircle has yet to publish trial data. The
company says it’s in the process of completing a paper for
submission to peer-reviewed scientific journals.
The technology Minicircle is relying on isn’t entirely
novel. Plasmids are a common tool of biotech researchers. India’s two-dose Covid-19 vaccine used them.
Scientists, however, have struggled to figure out how
to manufacture plasmids that can maintain the effects
of a therapy for long periods. Minicircle says it’s developed proprietary technology and manufacturing methods that address those problems. But the company has
declined to reveal the nature of the advances, saying it’s
trying to secure patents. “It took us a very long while to
figure this out,” Patterson says.
Johnson was, in many ways, far from the ideal candidate for the therapy. Different people respond to the
injection in different ways, though the most obvious
gains should present themselves in people who are out
of shape or older. Johnson, who’s 46, is very much in
shape, and the metrics that come back on his body tend
to describe a man many years younger. Neither he nor
the Minicircle founders knew what might happen to his
body post injection, though there was playful speculation that his muscles might grow muscles of their own.
Johnson and his main doctor, Oliver Zolman, had
identified follistatin as something worth trying. They’d
created a list of 20 or so of the more radical treatments
with supposed longevity benefits and done a risk-benefit
analysis on them. Follistatin ranked No. 7 for benefits
but had a lower risk profile than the candidates ahead
of it. In the months leading up to the injection, Johnson
and Zolman peppered the Minicircle team with questions and had scientists and a former FDA official do
the same. The answers were good enough for Johnson
to give it a try.
For Minicircle, Johnson’s arrival on Roatán could
have the clear benefit of making more people aware of
its technology. The company opted not to charge him
for the therapy even though he’s worth hundreds of millions of dollars and could certainly afford it. “He’s by far
the most high-profile person to come down here,” Davis
said before the procedure. “Bryan is giving us something
worth more than what we would charge him.” But there
was a risk for the company, too. Johnson measures his
body more than any other human, and he publishes
everything about his methods and their results publicly. “We’re going to reveal things they haven’t known
themselves,” he says. “This could be a positive, and it
could be a negative, because it could have effects that
you don’t want to see.”
Beyond any unexpected results, Johnson and his
celebrity also came with baggage. His former fiancée,
Taryn Southern, filed a lawsuit against him a few years
ago, claiming that she endured emotional trauma and
INJECTIONS
needle. The poking took just a few seconds, and that
was that. Johnson thanked the doctor and produced a
giant smile. Meanwhile, people in the room waited for
Johnson to either collapse or run out into the parking lot
and start lifting cars. Neither of these things happened.
Within a few weeks, Johnson flew to the Bahamas
for an injection of mesenchymal stem cells—No. 34 on
his therapeutic adventure list. Speaking just after that
trip from his home in Venice, California, he pulls up
a chart showing two years’ worth of data tracking his
aging markers and the effects various therapies had on
his body. The overall trend line shows his pace of aging
slowing, but in one instance a human growth hormone
boost designed to rejuvenate his thymus had caused
aging spikes. “That was successful because it helped my
thymus, but it wasn’t free,” Johnson says. “This aging
game is like whack-a-mole.”
A recent blood test revealed a 160% spike in Johnson’s
follistatin levels. But he hadn’t yet experienced any extra
endurance or set new personal records while working
out. Patterson considers this normal. “It compounds
over time,” he says. “I do expect that in the next few
months he’ll start noticing things.”
Johnson did have one post-follistatin revelation. He
could now rip his T-shirt in half with his bare hands. And
there’s an Instagram post to prove it. <BW>
DEEEEECEMBER 2023
Brimen and his lawyers are fighting this legal battle
and trying to raise more money for Próspera at the same
time. Brimen says he’s determined to make Próspera
a success and a model that, he hopes, can give rise to
similar zones all over the world. “I believe in human liberty,” he says. “I believe that you ought to have the freedom to make your own decisions, including taking risks.”
Johnson’s medical procedure took place at the Garm
clinic a few miles away from Próspera proper. The
clinic, which operates under Próspera’s charter, sits at
the water’s edge next to another idyllic Roatán resort.
Garm is run by Glenn Terry, an American orthopedic
surgeon and sports medicine specialist; it offers a wide
range of treatments, from hyperbaric oxygen therapy to
IVs full of stem cells, under the marketing tag line “Feel
Better, Live Better.”
Johnson and his videographer bounded into the
clinic with even more pep than usual and were greeted
by Terry, Patterson and Davis. The Minicircle founders
made Johnson slow his roll for a few minutes as they had
him read some legal paperwork and demonstrate he’s of
sober mind while giving his consent. Johnson’s response,
paraphrased: yes, fine, whatever.
The actual injection was anticlimactic. Johnson lifted
his shirt to reveal a festival of abs, and Terry hunted
around for a tiny pocket of fat where he could jab a
37
JOHNSON RECORDING
A VIDEO FOR HIS FANS
COSMETICS
THE SCIENTIFICATION
OF SKIN CARE
DEEEEEECEMBER 2023
Slowing the signs of aging
has become Job 1 for cosmetics
makers, who lure consumers
by trumpeting ingredients that
sound like something
straight out of a laboratory
By Jeannette Neumann
Illustrations by Lennard Kok
38
THE LOOOOOONGEVITY ISSUE
W
hen Heather Rogers’ 13-year-old daughter recently
said that all she wanted for Christmas was a skincare product with hyaluronic acid, Rogers said she’d
had enough.
“I said, ‘No, you just need sunscreen, and you
need to close your mouth,’ ” says Rogers, who’s a
board-certified dermatologist in Seattle. She says her daughter’s request is emblematic of Americans’ growing obsession
with buying products that have a main ingredient that sounds
straight out of a laboratory. Better still if it pledges to hydrate,
strengthen the “skin barrier” or, above all, slow the signs of aging.
Beauty companies big and small are increasingly using
science—or at least words and phrases that sound like they’re
pulled from a peer-reviewed journal—to market their products. The dollar value of products sold in the US that say they
include clinical ingredients, such as niacinamide and hyaluronic
acid (both can help hydrate skin), has been growing at an average annual rate of 71.5% during the past five years versus 5.3%
for overall skin-care items, says Jacqueline Flam Stokes, senior
vice president for beauty, drug and over-the-counter retail at
NielsenIQ, a data firm. The surge in demand for ingredient-led
products has surpassed consumer interest in beauty items marketed as “natural” or “organic,” which were particularly popular
before the pandemic, she says.
Take ceramides, lipid molecules that can help preserve moisture and protect against skin irritation. “Ceramides have been
a very popular ingredient in cosmetics and skin-care products
for decades,” Flam Stokes says. “What we’ve seen over the last
three years, really, is that ceramides are now a popular ingredient that’s being called out on the front of packing labels.”
Welcome to the scientification of skin care. The trend gathered
momentum during the pandemic, when Americans were spending
countless hours eyeing themselves on video chats. That prodded
many to try to address their perceived skin imperfections. With
guidance from skin-care influencers on TikTok and elsewhere,
shoppers snapped up clinical-sounding beauty products to
expand their facial routines to half a dozen steps or more.
“There’s a big focus on ingredients,” says Janet Pardo, senior
vice president for product development at Clinique and Origins,
Estée Lauder Cos. brands. “It’s how we market it now.”
The skin-care-cum-science trend is generating billions of dollars in sales for big cosmetics makers such as Estée Lauder and
L’Oréal SA, as well as for smaller companies. It’s also transforming the way Americans take care of their face and body, birthing
a generation of pseudo-dermatologists who pepper talk of their
skin-care routine with terms like “peptides” and “glycolic acid”
and phrases such as “transepidermal water loss.” It’s even leading some companies to pitch collagen-spiced holiday cocktails.
“As a doctor, I think it’s terrible,” says Rogers, the dermatologist.
Consumer enthusiasm for applying multiple products that each
focus on a single ingredient has increased the number of patients
who come to her with irritated skin. Many of the skin-care items
contain preservatives to prevent unwanted organisms from growing in the products, but they can also kill good ones that help the
skin. “All of these individual ingredients are not helpful by themselves,” she says. “Eating raw eggs is horrible, but cookies are
amazing,” she adds, by way of analogy.
Rogers tells her patients to avoid the many-step routines that
are popular on social media and just use face wash, a morning and
evening treatment to prevent or correct any damage, moisturizer
and, most important, sunscreen. Nyakio Grieco, founder of the
skin-care brand Relevant, agrees: “You don’t have to put every single thing and the kitchen sink—or the science lab—on your skin.”
For now, though, cosmetics companies are doubling down on
scientification. And the latest beauty buzzword is longevity. It’s
“the new frontier for skin care,” says Estée Lauder Senior Vice
President Jennifer Palmer, and “one of the hottest trends.”
While the term “anti-aging” targets a specific older demographic and can have a negative connotation—presenting
aging as something to be fought against—promoting longevity
SLOW THE CLOCK ON SKIN AG
NT TOHERE’S
A
WHAT’S NEW … AND THE TRIED AND TRUE I
NG
W
?
COSMETICS
about the products they’ve been using in the past couple of years.
“People became little mini scientists,” Del Campo says. “That’s
great—as long as people aren’t doing harm.”
As consumers gather knowledge about what skin-care items
they need, or think they need, their demands are becoming
increasingly specific. That’s led to some commodification, always
a hurdle for brands. If shoppers are looking for a serum with
15% vitamin C or 1% retinol, for example, does it matter where
or from whom they buy it if the ingredient is the same? “What’s
more important—the ingredient or the brand?” Flam Stokes asks.
“How do brands differentiate themselves?”
Some beauty brands are trying to stand out by listing several of
the sought-after ingredients their product contains. That presents
its own challenge on product packaging, notes Raymond James
analyst Olivia Tong. “You’re going to have 4-point font soon to
try to fit every bit of detail on there,” she says. “Just saying ‘dramatically different moisturizing lotion’ isn’t enough anymore.” <BW>
DEEEEEECEMBER 2023
in beauty flirts with the promise of extended vitality. And that’s
desired at any age.
In January, Estée Lauder will introduce a product called
Re-Nutriv Ultimate Diamond Transformative Brilliance Soft
Crème, with Sirtivity-LP. The product has sirtuins, which the brand
describes as “longevity proteins.” It will cost $350 for 1.7 ounces.
“We think it’s extremely relevant, trending and important to the
luxury customer, who is in particular seeming to over-index and
invest in longevity solutions,” Palmer says. “We believe in empowering our consumer with information and with the science.”
L’Oréal is also betting on the trend with Lancôme’s $270-anounce Absolue serum. On its website, the company says the
product is “inspired by a promising field of research called longevity science, which studies innovative ways to extend the
human lifespan, thereby achieving the dream of eternal youth.”
Danilo C. Del Campo, a board-certified dermatologist in
Chicago, welcomes the idea that his patients are learning more
MULTISTEP FACIALS
Combo treatments using new techniques
to cleanse, exfoliate, extract impurities and
hydrate skin can cost up to $350. They’re
often combined with infusions of antioxidants. While they frequently show immediate results in terms of skin hydration and
radiance, the anti-aging benefits of multistep regimens “are yet to be fully established,” says dermatologist Del Campo.
COLLAGEN SUPPLEMENTS
Collagen—a protein that helps maintain
skin elasticity and volume—drew buzz
among social media influencers thanks to
a 2021 analysis linking it to improvement in
the firmness of skin and a reduction of visible wrinkles. But a Harvard Medical School
report says it’s unclear whether those benefits were actually due to collagen rather
than other ingredients in the supplements.
LASER TREATMENTS
An “ablative” procedure uses an intense
beam of light to remove the top layer of
skin and heat the underlying dermis to
stimulate collagen production—resulting in
better tone and texture, according to the
Mayo Clinic. You’ll need weeks or months
of recovery, but the results can last years.
A nonablative course requires less recovery but isn’t as effective for wrinkles.
DAILY SUNSCREEN
This is the anti-aging basic increasingly
recommended for people of any age. “The
sun is radiation that breaks down collagen,
forms brown spots, breaks blood vessels
and causes skin cancer, so daily sunscreen is imperative,” says dermatologist
Rogers. Use SPF 30 or higher.
TOPICAL RETINOIDS
These vitamin A derivatives, long used to
treat pimples, also stimulate collagen production. They’re mostly prescription meds
such as tretinoin, which is approved for
acne and signs of aging like fine lines and
wrinkles. Less-potent adapalene, sold over
the counter, might not irritate as much.
HEALTHY LIFESTYLE CHOICES
Some of the most boring-but-effective
treatments to keep skin looking young
have been around for ages, including
maintaining a good diet, staying hydrated
and ditching cigarettes. “Smoking in particular accelerates the aging process,”
Del Campo says.
THE LOOOOOONGEVITY ISSUE
39
Bloomberg Businessweek
Month 00, 2023
CREDITS CREDITS CREDITS
40
Scientists and startups are trying to figure out how to control a woman’s biological clock.
If they do, it could also unlock the key to aging
By Kristen V. Brown Photograph by Amanda Savinon
PAUSING
ME
NO AU E
P S
41
HORMONE THERAPY
DEEEEEEEMBER 2023
W
hen David Pepin dissected the mouse on a dark
fall afternoon in 2013, he couldn’t believe what
he saw. As he pushed the kidneys aside to get
to the ovaries, he noticed something strange.
“They looked like neonatal ovaries,” Pepin recalls. They
were the size he’d expect to see in a newborn female,
not an adult. “They were miniature.”
Pepin, then a postdoc at Massachusetts General
Hospital in Boston, had seen enough mouse ovaries to
know that something unusual had happened. In a second mouse he found the same thing. The mice had
been treated with anti-müllerian hormone, or AMH, a
once-overlooked hormone produced by both the testicles
and the ovaries that helps regulate the development of
eggs in women. Pepin and his mentor, Patricia Donahoe,
thought AMH might help treat ovarian cancer, so they’d
given immunocompromised mice ovarian tumors and
then a gene therapy containing AMH. But Pepin, who
has a background in reproductive development, had a
hunch the AMH might do something else, too. In prior
experiments, researchers had blocked mice’s ability to
produce AMH and found their ovaries aged slightly faster.
But after removing the tumors from the first mouse, the
outcome was clear: The ovaries had shrunk.
A few days later, peering into a microscope at a cross
section of the mouse’s ovaries, he discovered why.
Follicles, the fluid-filled sacs that contain a developing
egg, grow, mature and then die. But this set of ovaries
had none of the large, mature follicles you’d expect in
42
an adult mouse. It contained only tiny primordial ones,
the kind that remain dormant until they are recruited
to mature. The AMH appeared to result in some sort
of arrested development; the cycle of growth and
death had been halted, leaving the pool of potential
future eggs intact and almost returning them to their
newborn state.
Immediately, Pepin says, it was clear that this hormone had a powerful sway over the reproductive system,
far more so than previously realized. AMH might be able
to slow the aging of the reproductive system, extending the window of fertility and staving off menopause.
“It was basically Benjamin Button, going backwards,”
he says. “I was like, ‘OK, something big is happening.’ ”
S
cience has given the modern woman
incredible tools to control her reproductive
destiny. The most obvious is the birth control pill, introduced in 1960 to stop ovulation
using hormones. Replacing rudimentary cervical caps and rubber diaphragms, it allowed a woman
to modulate her ability to get pregnant with scientific
precision. Today’s tools mainly help to turn off the capabilities of the reproductive system. Technologies like
in vitro fertilization can help when there are snags in
the reproductive machinery, such as blocked fallopian
tubes or uterine fibroids. But women are born with all
the eggs they’ll ever have, and when they’re gone—at
an average age of 51—the time on their biological clock
is officially up.
At that point, the production of hormones including estrogen and progesterone drops dramatically,
SUH: PHOTOGRAPH BY LAUREL GOLIO FOR BLOOMBERG BUSINESSWEEK. PEPIN: PHOTOGRAPH BY PHILIP KEITH FOR BLOOMBERG BUSINESSWEEK
THE LOOOOOOONGEVITY ISSUE
YOUSIN SUH IN HER
LAB AT COLUMBIA
DEEEEEEEMBER 2023
43
THE LOOOOOOONGEVITY ISSUE
culminating in a massive, sudden biological
change. Ovarian hormones regulate not only
reproduction, but also things such as bone
mass, blood sugar, brain function and cholesterol. The result is often a slew of uncomfortable symptoms—hot flashes, weight gain and
mood changes—as well as a marked increase in
health risks including heart disease, osteoporosis and dementia. Pregnancy also becomes
impossible, though for most women infertility
happens years before, when they’re in their
mid-40s. This fate befalls anyone with ovaries—
cisgender women, as well as nonbinary people and trans men. The ovaries age much faster
than the rest of the body, until, one day in middle age, they basically stop functioning altogether. There is no pill that can intervene when
they start shutting down. At least not yet.
A surge of interest in both longevity research PEPIN IN HIS LAB
and women’s health has finally started to AT MASSACHUSETTS
GENERAL
change that. “This is the area where there has
been no funding and no interest until recently,” says to study aging.” Watching the ovaries age is a little like
Yousin Suh, a researcher studying ovarian aging at listening to a podcast at double speed, which is why
Columbia University Irving Medical Center in New York the ovary could even become a proving ground for lonCity. Long-standing gender bias in medicine has left the gevity drugs, a therapeutics market expected to reach
female reproductive system woefully understudied. (In more than $44 billion within the next decade. This could
the US, it’s been a requirement to include women in have benefits for everyone, since most of the developed
clinical trials since only 1993, and the study of so-called world’s biggest killers for men and women—heart diswomen’s diseases is historically underfunded.)
ease, stroke, cancer, dementia—are diseases for which
As Pepin and other scientists finally begin to unravel age is the main risk factor.
what makes the reproductive system age so rapidly,
Scientists and startups are racing to turn these revthey’re also uncovering a tantalizing possibility: There elations into therapies that could one day advance
may be ways to slow that aging down. Not only could this treatment for menopause and infertility and perhaps
extend a woman’s childbearing years, it could dramati- eventually intervene in the process of aging itself.
cally improve women’s health, staving off the ill effects Williams and Suh have already begun enrolling women
associated with the onset of menopause. Research has in a clinical trial to test whether rapamycin—an immushown that women who go through menopause later nosuppressant typically used in organ transplants
in life tend to live longer. While women generally out- and cancer treatment that’s also become a popular
live men, they also are more likely to spend their later anti-aging drug—might also slow aging of the ovaries.
years in poor health, more often suffering from multiple Researchers at Northwestern University are exploring
chronic conditions at once. “The ovary has this protec- whether anti-fibrotic drugs could improve the quality of
tive benefit,” says Zev Williams, director of the Columbia a woman’s eggs as she ages as well as improve reproducUniversity Fertility Center and a collaborator in Suh’s tive longevity itself. A startup called Gameto has used
research. “It’s lost when menopause begins.”
stem cell science to create a less intensive version of IVF
What’s not clear is why ovaries age as rapidly as and plans to use the same technology to create better
they do. Understanding that could help uncover how menopause therapies.
and why aging occurs at all. “Normally aging has to be
Two-and-a-half years ago, Pepin, along with Donahoe
studied over decades to be able to have measurable and Harvard University Ph.D. Daisy Robinton, founded
changes,” Williams says. “The ovary is an ideal model Oviva Therapeutics Inc. with funding from aging-focused
drug development company Cambrian BioPharma Inc.
Their goal: to turn AMH into treatments that could
improve ovarian function and extend life span. In the
universe of aging research, Pepin says, the ovary just
might be low-hanging fruit. It’s a far smaller task to
intervene in the aging of one organ versus the entire
body. “If you’re trying to extend longevity, that’s hard,”
Pepin says. “But the ovary is really weird. It starts to
degenerate way earlier than anything else. So even if
you didn’t touch anything else, you could easily see an
effect on the ovary.”
44
THE LOOOOOOONGEVITY ISSUE
The global fertility market, worth about $35.2 billion
last year, is expected to grow to $84 billion by 2028,
according to market research firm Imarc Group. Oviva
raised $11.5 million in May 2022 for an early-stage treatment that will aim to improve fertility treatments by
helping patients increase the number of eggs in each
cycle. Eventually, Oviva hopes to pull off a feat that
seems almost unimaginable: giving women a drug that
will allow them to choose when—and whether—they
go through menopause. At a time when politicians
are eroding women’s hard-won reproductive choices,
Oviva’s founders want to give them even more control. “I see it very much akin to how the contraceptive
pill really changed the game for women in the ’70s,”
Robinton says.
H
uman females are the odd ones out in terms
of the reproductive life cycle. Most mammals
are fertile right up to the end of their lives. The
only other mammals that go through menopause are a few species of whales and, depending on whom you ask, some great apes. No one
is even quite sure why menopause occurs at all. Perhaps
the most popular theory is the “grandmother hypothesis,” which argues there’s an evolutionary benefit: Older
women, no longer in their reproductive years, help care
for grandchildren, boosting the kids’ chances of survival.
For much of modern medical human history, the end
of a woman’s reproductive years has been regarded as
just that, an oddity. Worse, modern cultural stereotypes
portray postmenopausal women as sexually undesirable
and fragile. In the movie Sex and the City 2, the character
Samantha Jones turns to an assortment of pills, patches
and hormone therapies to slow the march toward irrelevance. In the British sitcom Absolutely Fabulous, talking
about all of menopause’s terrible symptoms is so loathed
by the main characters that they require an anonymous
support group. Historically, the postmenopausal woman
has often been portrayed as some combination of mystical, monstrous and deadly. In the Victorian era, physicians believed menopause made women insane. Those
suffering noticeable symptoms might be locked away
in an asylum. Sometimes doctors removed the ovaries
altogether, believing that if they were no longer functioning, they were diseased. The operation often only
worsened any symptoms.
Eventually, medical science advanced, developing
blunt instruments that could bend the female reproductive system to our will. The workings of the endocrine
system were discovered, and ovarian hormones including estrogen and progesterone were isolated, leading
to the development of the birth control pill as well as
hormonal treatments that replace some of the body’s
waning hormones to dull menopausal effects. With the
development of IVF, the need to understand many of
the basics of human reproduction became less urgent.
When it comes to ovarian aging, some of the fundamentals are still elusive. For example, once a woman
hits her 30s, the ovaries’ rate of aging seems to accelerate rapidly. Why does it do that? And primordial follicles
seem to remain in a sort of sleeper state until it’s their
turn to mature. What activates them? “It’s like a black
box,” says Jennifer Garrison, a neuroscientist at the
Buck Institute for Research on Aging in Marin County,
California. “We don’t understand the most basic things
about how the system works.”
Much of the research that’s formed the basis of reproductive longevity came out of an effort to preserve the
PHOTOGRAPH BY ELIZABETH WEINBERG FOR BLOOMBERG BUSINESSWEEK
HORMONE THERAPY
DEEEEEEEMBER 2023
“All I was thinking about was
how our ovaries stop working
halfway through our lives
and that in any room I had been
in that was focused on aging,
no one had brought this up”
THE LOOOOOOONGEVITY ISSUE
DEEEEEEEMBER 2023
HORMONE THERAPY
ROBINTON
45
LICL
L
E
THE LIFE CYCLE OF A FO
1 The tiny, dormant follicles
women are born with contain a
single oocyte (the cell that forms
an egg) that’s surrounded by pregranulosa cells. These eventually
provide nutrients and send signals
to the oocyte.
2 When a primordial follicle
wakes up, it becomes a primary
follicle. From before birth until
menopause, follicles are recruited
to begin growing and developing.
The oocyte gets bigger, and
pre-granulosa cells activate to
become true granulosa cells.
THE LOOOOOOONGEVITY ISSUE
for work like hers and Pepin’s to flourish. In 2018,
Nicole Shanahan, an attorney, philanthropist and (most
famously) the former wife of Google co-founder Sergey
Brin, approached the Buck Institute. After contemplating IVF, then conceiving naturally, Shanahan’s experience made her realize something was deeply wrong with
the medical understanding of fertility. She gave the Buck
Institute $6 million to start its Center for Reproductive
Longevity and Equality, and the following year she
helped create its grant-giving arm for researchers at
other institutions to study the topic. “No one has ever
funded foundational science in reproductive aging or
ovarian function,” Shanahan says. “It is the least funded
organ by a significant amount.”
Recasting the problem as one of aging—not just
fertility—has finally helped propel the area of study, says
Francesca Duncan, a reproductive biologist who studies ovarian aging at Northwestern. “It’s a small field, but
at least we’re literally a field now,” she says, noting that
the new angle also has helped attract more research
dollars. “Yes, it is about fertility, but it’s not just about
fertility,” she says. “It’s about endocrine health and general health at the same time.”
3 The follicle grows. A thick
layer develops around the
oocyte, and the follicle begins to
develop a theca. Akin to a shell,
it’s responsible for hormone
production, among other things.
4 Growth continues and a fluidfilled cavity called the antrum
forms.
5 This is the last stage of a
mature follicle before ovulation.
Typically, just one dominant
follicle is selected to fully mature
every month.
6 During ovulation, the now
mature egg detaches itself
from the rest of the follicle. The
follicle releases hormones, such
as progesterone, that prepare
the body for ovulation, and
eventually it ruptures, releasing
the egg to begin its journey to the
fallopian tube.
7 Ovulation marks the end of
what’s known as the follicular
phase and the start of the luteal
phase, in which remnants of
the dominant follicle begin to
transform into a new structure
called the corpus luteum.
8 This is a cyst that plays an
important role in producing
hormones, such as progesterone,
that help maintain pregnancy.
9 When pregnancy doesn’t
occur, this cyst disappears.
The lining of the uterus is shed
during menstruation, and the
cycle repeats.
PHOTOGRAPH BY LAUREL GOLIO FOR BLOOMBERG BUSINESSWEEK. ILLUSTRATION BY CHRIS PHILPOT
HORMONE THERAPY
DEEEEEEEMBER 2023
46
fertility of women diagnosed with cancer. Treatments
like chemotherapy often, as a side effect, strip women
of their ability to bear children. Egg freezing, in which
the eggs are harvested and stored for later, is one way to
preserve fertility. But it doesn’t work for every woman,
including those who haven’t yet gone through puberty.
In 2004, Belgian doctors announced a first: A woman
whose reproductive system had been destroyed by cancer treatments gave birth. Doctors had cut out a piece of
her ovarian tissue and frozen it, then grafted it back into
her body years later. The proof that it had kick-started
her reproductive system was the healthy baby girl. Since
then, thousands of girls and women have had their ovarian tissue cryopreserved.
To Garrison, this is a sign that the hormone cocktail produced by the female reproductive system might
potentially be controlled. She studies what she calls the
brain’s Wi-Fi—its ability to send long-range signals, such
as those between the brain and the ovaries. She wants
to understand how changes with age in that communication might “give us a clue about aging in the rest of
the body.” More than that, she wants to create space
DEEEEEEEMBER 2023
A
47
THE LOOOOOOONGEVITY ISSUE
t 31, Daisy Robinton
suddenly found herself confronted by
the incessant, inevitable ticking of her
biological clock.
It was 2019, and
she’d recently finished her postdoc at Boston Children’s Hospital
researching the cellular interaction at the root of neurodegenerative diseases. She’d also just
ended a five-year relationship and
moved to New York City. Her work
had received attention, including a
popular TedX London talk on the
science of aging, but the lab, she
realized, wasn’t for her. She didn’t
quite know what she wanted to do
professionally—she was making a
A SCREEN IN SUH’S LAB
living with a combination of scien- OF GENETICALLY MODIFIED
tific consulting and fashion model- CELLS THAT ARE COMMON
IN THE OVARY
ing. She did know that she wanted a
family. So she set up an appointment with a reproductive the number of a woman’s eggs decreases, eventually
endocrinologist to explore freezing her eggs. She walked to zero. The general wisdom is that a human female
away reassured by the state of her own reproductive sys- is born with 1 million to 2 million eggs, and more than
tem but furious at the state of women’s health.
half are gone by the time she even hits puberty. When
Around this time, she happened to reconnect with she reaches her 30s, not only does she have just a fracstem cell biologist James Peyer, whom she’d once met at tion of those eggs left, but the quality of the remaining
an entrepreneurship event and who’d recently started ones has declined steeply. That’s the second problem:
Cambrian Bio. Over coffee, he told her about his com- Older eggs are more likely to contain genetic abnormalpany. “All I was thinking about was how our ovaries stop ities, one reason miscarriages become more common
working halfway through our lives and that in any room with age. Then there’s the third problem, which has to
I had been in that was focused on aging, no one had do with the environment of the ovary itself: Over time
brought this up,” says Robinton. “It was shocking to me. it becomes fibrotic, stiffening and making it harder for
I just thought it was stupid and rude and horrifying.”
healthy eggs to grow. “If you can solve all these probPeyer hired Robinton as a staff scientist to hunt for lems, then maybe you can slow down ovarian aging,”
a way to turn her outrage into a capitalist endeavor. In Pepin says.
fall 2020 she organized a virtual summit on reproductive
The work that could most immediately benefit
longevity where someone mentioned Pepin’s research. women primarily focuses on the first problem. When
It seemed to mesh with an idea she was already explor- Pepin made his initial discovery, he thought AMH could
ing, that slowing the decline of the ovarian reserve could be the basis of a better birth control therapy. There are
also extend the lifetime of the ovaries. Robinton cold- receptors for estrogen all over the body, a reason so
emailed Pepin, and by the next year Oviva was born. “I many women experience a litany of side effects from
was looking to find a way to get this to the clinic, and taking the pill. But AMH receptors are limited to the
she was looking for things that she could bring to the reproductive system, the nearby adrenal glands and a
clinic,” Pepin says.
small part of the brain that modulates reproduction.
To solve the issue of the aging ovaries, three key AMH, Pepin says, also seems to be the only known horproblems will need to be addressed. The first is that mone that can inhibit the growth of primordial follicles,
the pool of those waiting to develop.
That’s what made him think a decade ago that it also
could help protect the fertility of those undergoing cancer treatment, which he initially demonstrated in mice.
But, more recently, Pepin has shown that AMH can be
used to create what’s basically a permanent birth control in cats. Working with the Cincinnati Zoo, he tested
an AMH gene therapy on cats that halts ovulation. (He
envisions it as an alternative to spaying, an invasive
surgery in which female cats usually lose not just the
ovaries but their uterus, too.) If you could dial that
THE LOOOOOOONGEVITY ISSUE
A PIPETTE, A LAB
ESSENTIAL IN
SUH’S STUDY OF
HOW CELLS RESPOND
TO RAPAMYCIN
therapy down and turn it into, say, a pill—a difficult
feat—then perhaps it could be used to slow the attrition
of eggs from women’s resting pool.
Prolonging the depletion of a woman’s eggs could
delay the march toward menopause, keeping up the
body’s production of critical ovarian hormones for a
longer period. In older experiments, when researchers transplanted the ovaries of younger mice into older
ones, they lived about 40% longer and also appeared
to have healthier hearts. (Mice, of course, do not go
through menopause, making them an imperfect model.)
But bringing any drug from benchtop to market is a
slog requiring time, uncertainty and millions of dollars.
“There is more risk, simply because it just hasn’t been
done,” says Cambrian’s Peyer. For Oviva’s AMH-based
therapy to make it to market, there’s also the problem
of the protein itself to solve. One reason it took so long
to figure out that AMH plays such a huge role in reproduction is that it’s difficult to produce in any sort of
quantity. Estrogen, the first reproductive hormone isolated, in 1929, is among the least complicated to make.
It’s physically small and structurally simple, making it
easy to synthesize in a lab. You can plop its synthetic
form into a pill, like birth control, and it will work.
AMH, in comparison, is massive in size, its structure
made up of intricate folds. For it to be activated, AMH has
PHOTOGRAPH BY LAUREL GOLIO FOR BLOOMBERG BUSINESSWEEK
48
to be cleaved precisely so that its two
halves are separated but still in contact.
The body does that naturally, but the
process is too complex to synthesize.
To produce it, you have to program
mammalian cells to make AMH for you,
creating what’s known as a recombinant protein, a protein produced by a
host organism—in Pepin’s case, Chinese
hamster ovarian cells. Figuring out how
to do this was one of his first big breakthroughs as a postdoc.
Pepin’s cat contraceptive relies on
this engineered AMH, a form of the protein close to the
original. So will Oviva’s first human therapy, but this drug
will amp up reproductive ability, not shut it down. The
purpose is to help women going through IVF and egg freezing who are poor responders to traditional ovarian stimulation. The hope is to get them to produce larger quantities
of eggs, which could improve the success rates of egg
retrieval procedures that are intensive and expensive.
Such a drug, Robinton says, would show that AMH’s
ability to influence the reproductive system can translate from mice and cats into humans in an already
proven market. From there, Robinton says, Oviva can
eventually tackle the bigger goal: delaying menopause.
To achieve that, the complicated AMH protein will need
to be altered further, turned into a new drug that is less
painful than a jab, and virtually side-effect free, which
throws novel challenges into the mix. “When I use the
gene therapy, I’m using the natural hormone,” Pepin
says. “I’ve modified it, but only a little bit. It’s very safe.”
Turning that natural hormone into a drug compound,
he says, means more unknowns, including side effects.
While major drugmakers have largely avoided AMH
drugs, at least in part because of their complexity, the
possibilities for the hormone also extend to contraception and treatments for polycystic ovarian syndrome and
cancers of the reproductive tract. Celmatix, an early-stage
A
MH is only one potential way into
manipulating the ovary. At Columbia,
Suh and Williams are enrolling about
50 women for a pilot study to see how
the decades-old organ transplant
drug rapamycin affects ovarian aging.
Rapamycin acts on the body’s mTOR
pathway, a buzzword in longevity
circles: Activation of the mTOR pathway seems to be
associated with aging, suggesting that intervening in it
could slow the process. But it also seems to play a role
in the activation of primordial follicles, which raises the
question of whether targeting the mTOR pathway could
reduce the rate at which those follicles mature. Kara
Goldman, Northwestern’s medical director of fertility
preservation and an associate professor, has explored
how mTOR-inhibiting drugs could protect mice from
the rapid depletion of eggs caused by cancer treatments. Now Suh and Williams are applying that work
to humans. “We are really confident that rapamycin can
help women to delay aging in the ovary, thereby improving aging in the body,” Suh says.
When you compare older ovaries to younger ones,
she says, the signaling of the mTOR pathway is “screaming high.” At a molecular level, she says, the cells of
the ovaries resembled cells from other tissues in people twice as old. With intervention, Williams says, “in a
regular month, instead of losing, let’s say, 15 eggs, you
lose, let’s say, eight. So you’ve slowed down the rate at
which you’re using up eggs.”
But only slowing the depleting of the pool won’t necessarily extend a woman’s fertile years. To do that, you
probably need to solve the other two problems: egg
quality and the quality of the ovarian environment. “If
your nest is crappy, your eggs are going to be crappy,”
says Northwestern’s Duncan. She says ovarian stiffness
affects how the follicles grow, the caliber of the eggs
inside of them and the chances for ovulation to occur.
So far, Duncan has shown how low doses of anti-fibrotic drugs in mice could successfully intervene. But
scientists like her are just beginning to untangle all the
complex signaling involved in reproductive function,
from understanding the pathway responsible for fibrosis of the ovary to whether a bigger pool of eggs also
HORMONE THERAPY
DEEEEEEEMBER 2023
ovarian drug company, also has an AMH-based drug in
its pipeline. It’s focused on preserving ovarian function
during cancer treatment. As Celmatix founder and chief
executive officer Piraye Yurttas Beim says: “The applications for AMH are basically endless.”
helps improve egg quality and deter ovarian stiffness.
Garrison, the Buck Institute neuroscientist, says she
hopes that studying the signals between the brain and
the ovaries themselves can finally bring an understanding of what’s in the black box. “If we could increase
the number of healthy eggs the woman has by 1% or
2% when she’s at age 40, that would maybe on average
push out the age of menopause by five or 10 years. That
would be profound,” she says. “We could give women
the ability to make choices about their life in the same
way that men do.”
Of course, because we don’t know why menopause
occurs, we don’t know what would happen if it didn’t.
Stephanie Faubion, the medical director for the North
American Menopause Society, says she’s not sure delaying menopause would make a difference in women’s
overall health. The association of some health problems
with menopause, she says, may simply be correlation,
not causation. “We’ve already tried using hormone therapy, and it didn’t prevent heart disease,” she says, noting that it could even have a negative effect.
Getting to the bottom of these reproductive aging
questions requires money, another challenge for an
industry where there isn’t always obvious intellectual
property. Take rapamycin. Since it’s a generic drug,
finding out that it can slow human ovarian aging would
be a huge scientific discovery without a windfall. Bigger
trials will require bigger funding, and it’s unclear where
that money will come from. “The challenge with the
medication being generic and low-cost is that there isn’t
industry funding for the work,” Williams says. “The support would likely need to come from philanthropy or
[the National Institutes of Health].” The more ovarian
aging research is recast as the first step in studying aging
more generally, the more potential it has for backers.
In the meantime, startups such as Oviva are working to make the leap from testing in animals to humans.
Robinton expects its AMH fertility drug could be
in human trials within a few years. And from where
Oviva is at, she says, a small molecule drug like the one
they’re developing could typically be in clinical trials in
as quickly as four years. Robinton envisions a not-toodistant future—maybe before she reaches menopause
herself—in which women will have therapeutic interventions that allow their ovaries to keep working for longer,
helping maintain the skin and hair and mood and health
and maybe even the sex life of their younger years. “For
me, the pie in the sky is really choosing when to have
the sun set on your ovaries,” she says.
Pepin is more reserved. There are still major safety
questions to answer, such as whether the ovary would
continue to perform all of its other critical functions if
you slowed down aging. He’s less bullish on the probability of one magic anti-aging pill for reproductive function. He thinks a solution might more likely combine
findings from all the different corners of the field. Who
knows whether we’ll be able to slow ovarian aging completely, he says, or merely intervene in certain facets of
it. “What I do know,” he says, “is we have a very good
contraceptive for cats.” <BW>
49
THE LOOOOOOONGEVITY ISSUE
“The pie in the sky is really
choosing when to have the sun
set on your ovaries”
HANDBOOK
A GUIDE TO
GROWI OLD
NG
DEEEEEEEECEMBER 2023
By Charley Locke
Illustrations by Lennard Kok
THE LOOOOOOOONGEVITY ISSUE
50
Americans are getting old. In 10 years,
there will be 78 million people in the
US over 65, outnumbering the population under 18 for the first time. And, of
course, aging Americans are reinventing the life stage to suit themselves, in
life and in pop culture: The glamorous
exploration of And Just Like That offers
a very different vision of the mid-50s
than the caftans and cheesecakes of
The Golden Girls does.
Yet despite efforts to stave off aging
(think supplements and preventive
Botox) or to reframe it (picture geriatric athleisure and chic canes), getting
old has some unavoidable downsides.
In a society that punishes admissions
of vulnerability, the specific indignities
and revelations of aging are mostly
kept private. There isn’t a user manual for an aging body. But there should
be. May we be so lucky, the big questions and the little ones—how to retire,
where to live, where to find love, how to
actually talk to your doctor—will come
for us all. Read on for some answers.
HANDBOOK
HOW TO HAVE
(GOOD) SEX
Arlene Heyman
doesn’t have time
for the usual squeamishness in this department.
“We’re alive until we’re dead, and we’re sexual beings
until death,” says Heyman, 81, author of the 2016
short story collection Scary Old Sex, among other
books. “People have absorbed from the culture an
image that they’re not supposed to do this when
they’re old, but why shouldn’t old people have sex?”
Once you’re past the initial hurdle of acknowledging your human urges, Heyman says, the
toughest part can be having to admit your
human frailty. “Nobody is their 19-year-old self
anymore, and you can’t have sex the same way,”
she says. Fortunately, that’s a problem that medicine has been very interested in solving. There are
plenty of products that can help with the common
bedroom hurdles: lubricants, Viagra, vaginal tablets. “Modify things if you have to, but don’t deprive
yourself,” Heyman says. “The point is to find ways
to get pleasure and give pleasure.”
Dating later in life brings two huge advantages:
You already know who you are, and the pressure
is off. Forget the delicate dance of second dates
you experienced in your 20s and 30s, evaluating
whether you share values around kids or money.
“In your 20s, you were building, but now you get
to play,” says Lisa Copeland, a dating coach who
works with women over 50.
An older dating pool comes with its own challenges, from deciphering changing social mores on
apps to meeting up during daylight hours so you can
avoid driving home in the dark. But the biggest hurdle
is developing confidence, especially after an unfulfilling marriage or significant time alone. Get rid of limiting beliefs about yourself—and about who’d be a
good match for you at this stage of life. “Often people are looking for their old type, but if your old type
worked for you, you’d still be with them,” Copeland
says. You’ve changed, and your ideal relationship
might have to as well. Know yourself, be open, and
put yourself out there. (And get a friend to approve
your picks for recent profile photos.)
DEEEEEEEECEMBER 2023
HOW TO
FIND LOVE AFTER 65
51
When it comes to where one should grow old, there
are two key things to consider: comfort and belonging, says Stephen Golant, who studies the geography of aging at the University of Florida. Think of
comfort as the practical aspects. Do you have stairs
in your home? Is there accessible public transportation nearby? Belonging is the emotional side. Do
you have friends or family around? Are you living in
a caring community? How do you spend your days?
For those who want to stay right where they
are, there’s some good news: With the prevalence
of on-demand services (from rides to groceries
to a helping hand) and technology that detects
falls, aging in place is getting easier. But the decision still requires some planning and some frank
conversations
with loved ones
on the early side.
“When you’re feeling active, healthy
and in shape, that
is the time to make
plans for how you
want to be cared
for when you’re less
independent,” Golant
says. “Don’t wait to
make these long-termcare decisions in a
crisis situation.”
THE LOOOOOOOONGEVITY ISSUE
HOW TO CHOOSE WHERE TO LIVE
HANDBOOK
HOW TO TALK TO
YOUR DOCTOR
DEEEEEEEECEMBER 2023
“I’m a doctor, and I have a hard time navigating
the health-care system,” says Mary Tinetti, 72,
who researches clinical decision-making for older
adults at the Yale School of Medicine. As you age,
one of your most important relationships will be with
your primary-care provider, so it’s worth choosing
them carefully. Do they listen to you? Do they ask
thorough questions? Do you feel comfortable asking them questions, or do they just talk at you?
Of course, it’s nearly impossible to get to everything in a 15-minute primary-care visit. (Tinetti stresses
that the experience is frustrating for the clinician, too.)
To make the most of the time, come prepared with a
written-out agenda of three questions, max, and share
them at the beginning of your appointment.
THE LOOOOOOOONGEVITY ISSUE
52
HOW TO DO
WN
SI
ZE
Start small, and do
it today. Maybe that
means taking a bag of old
winter jackets from the coat
closet to Goodwill. Maybe it means
dumping a stack of magazines in the recycling bin.
Maybe it means tossing your adult kids’ middle-school
art projects. The important thing is to start.
You can follow a guru like Marie Kondo if you
want, but the basic premise is the same: Get rid of
stuff you don’t actually use. The practical things
(unopened kitchen gadgets, ill-fitting clothes) are
easier; the sentimental items get tough. That’s
where some honest stage-of-life reflection comes
in. You may enjoy looking through old birthday
cards, but will your daughter want them? Which
items of your parents’ will hold meaning for your
son, and which will seem like estate-sale junk?
You may not be downsizing your home yet, but if
you don’t sort through a lifetime’s accumulation of
belongings, you’ll leave it as an unwelcome inheritance for your kids. (That means some hard limits
on what additional items you buy, too.)
HOW TO
STAY HEALTHY
It matters whether
you wore sunscreen, but you can still make a difference in your physical health now. You already know the
best advice: Sleep well, eat mostly healthy foods, move
your body every day, and drink alcohol in moderation
(or not at all). Otherwise, much of healthy aging comes
down to emotional and social health. Do you regularly
see friends? Do you have an active community? Are
there people who you rely on, and who rely on you?
TO ASK FOR HELP
HOW
None of us can go through life’s big transitions
alone. Aging is full of moments when we need to ask
for help, whether reading a menu in a dimly lighted
restaurant or signing up for Medicare. We know
there shouldn’t be any shame in asking for
help, but forming the question still makes us
feel vulnerable.
If you’re preparing for a difficult ask
around caregiving, ground the conversation in clear logistics and keep the emotions focused on you rather than them. For
example, “I feel overwhelmed at my doctor’s
appointments, and I’d like one of you to come
with me” will likely land better than “Neither of
you are taking good care of me and my health.”
Making a clear demand can feel awkward,
but remember that you likely won’t
get what you don’t ask for. Even
if you end up at a compromise
(coming to every other doctor’s appointment, for example), speaking up reminds
us that we’re in a community. “You’re really not alone,
even though it feels like it,”
says Rosemary Blieszner, who
recently retired from leading the
Center for Gerontology at Virginia
Tech. “It can be isolating, but reach
out and get some relief and advice.”
HANDBOOK
HOW TO FINANCIALLY PREPARE FOR RETIREMENT
Most financial planners suggest that to retire, your
lifetime income (Social Security, pensions, an annuity) should cover at least your basic needs. But
“there’s not a clear-cut conclusion, and it’s contextdependent,” says Gal Wettstein, senior research
economist at the Center for Retirement Research
at Boston College. “It’s important for people to plan
for living longer than they would think, because they
HOW TO
DEAL WITH
AGEISM
Age discrimination is pervasive, whether in
the workplace or
the grocery store or one’s
own family. As with any other
societal prejudice, the best way
to change it is to speak up and
challenge others’ assumptions. “First, you have to see
it and acknowledge that ageism is a thing,” says Tracey
Gendron, executive director of the Virginia Center
on Aging. “Then
we can educate
and reframe.”
That reframing can look different
tend to think too short—and because it’s so bad to
run out of money that you don’t want it to happen
even with a slim chance.”
As we live longer, many people are nearing retirement age and finding they don’t have enough money
set aside. It’s still not too late to prepare. You may want
to take on a part-time job in retirement, which also provides structure and community. If you’re not bringing
in additional funding, you’ll need to carefully manage
your cash flow. Many older adults downsize from a
family home to an apartment; those on a particularly
limited income with equity in their homes can always
take out a reverse mortgage.
depending on the context and your audience. If a
fellow runner patronizes you about being a serious
athlete “at your age,” you can tell them that that’s
small-minded and that physical ability isn’t dependent on age. If your grandchild is laughing at TikTok
videos of a confused grandmother, you can gently
ask them why that’s funny and explain how stereotypes can be hurtful.
Stay aware of how you perpetuate ageism, too—
saying someone’s haircut makes them look younger,
for example, or reassuring someone that they’re not
old, they’re just mature. “We disguise these microaggressions as compliments, but then we internalize those messages,” says Gendron.
Ageism can go both ways, too: Don’t judge anyone’s abilities based on their age. “If we assume that
someone is too young to be a supervisor or too old
to go to medical school, then we’re condoning ageism, not challenging it,” Gendron says.
DEEEEEEEECEMBER 2023
Forty years of 40-hour workweeks seems long. But
for those staring down an empty retirement, the
unknown can seem longer. “People feel like they’ve
reached their goals—raising their children, finishing
work as they’ve known it—but they never took the
time to figure out what they wanted,” says Karen
Midyet, a psychologist in Fort Collins, Colorado,
who treats adults age 50-103. “All of a sudden,
people have to ask, ’What is it that I want?’ ”
She suggests starting out by writing down
your values right now. Do you care about leaving a legacy for your family or in your profession?
Do you want to prioritize travel? Are you the caregiver for others, whether a spouse or a grandchild?
Next, think about structure. If you lived by a busy
calendar for 40 years, you likely won’t do well with
free-form days. “Even if you only start out by putting
in working out and meals for the day, add them to a
calendar,” Midyet says. You can build from there.
53
THE LOOOOOOOONGEVITY ISSUE
HOW TO HANDLE RETIRING
HANDBOOK
DEEEEEEEECEMBER 2023
HOW TO DEAL WITH
FORGETTING THINGS
Routine is your friend. Put your wallet, keys, phone
and glasses in the same place every time you walk
in the door.
54
HOW TO CARE FOR AN
OLDER PARENT
Establishing a
different relationship with a spouse or parents who traditionally
took care of you requires some frank conversations.
Have they made a will? What are their care directives for when they’re unable to make those decisions for themselves? Have they communicated
where to find important documents? “As an adult
child, it’s really difficult to bring up these conversations,” says Virginia Tech’s Blieszner. “You have to
try to find a way that would not be too off-putting.”
Lead with grace and clarity for the best results.
Blieszner adds that caregivers need community,
too. Support groups can be a great way to get candid advice and empathy from those who’ve been
through similar experiences, whether focused on living with a spouse with Alzheimer’s or an aunt going
through treatment for colon cancer. Remember, a
caregiver also needs to be cared for—which means
you should ask for specifics. “Other people might
not know what to do, so in a caregiving situation it’s
on you to ask for what you need,” says Blieszner.
Wish your wife’s brother would step in so you could
take an afternoon off? Ask him.
Additional challenges arise for seniors looking
after their elders. After decades of taking care of
kids and parents, the 60s and 70s should be a time
focused on your own health and care. But as more
people live into their 90s and beyond, an increasing number of seniors are spending retirement taking care of their own aging parents.
“When you have a parent that high in age, often
it’s a huge burden to the next generation, but it’s
hard to tell anybody that it’s very difficult,” says
Kathrin Boerner, a professor at the University of
Massachusetts at Boston who studies the care
relationship in older dyads, such as a 75-yearold child and their 98-year-old parent. She distinguishes between “young old” and “old old” people,
and emphasizes that the “young old” person in
these care relationships needs to also take care
of themselves. That means emotional support,
including finding others you can lean on when your
responsibilities become too much, and medical care.
“Ignoring your own health issues at 75 will have
serious consequences that put you on a less good
health trajectory than your parent, who did not have
that care responsibility,” says Boerner.
THE LOOOOOOOONGEVITY ISSUE
HOW TO MAKE FRIENDS
It’s normal for friendships to ebb and flow after big life
changes: graduating from high school, moving to a new
city, becoming a parent, changing careers. But it can be
particularly challenging for seniors to form and sustain
friendships as they lose independence and shift routines.
“Older adults may no longer go into the office or out into
the community as they normally did, and they can fall
out of habits and rituals that used to keep them socially
engaged,” says Kasley Killam, who studies loneliness and
social health at Social Health Labs in Southern California.
That can make it hard to recover from the loneliness when
friends begin to pass away.
Killam advises thinking about social health just as you
think about physical health. Commit to repeating small
actions every day, such as making a short phone call, saying
hello to a neighbor or stopping by your local coffee shop
or rec center on a daily walk. “Think about these steps as
core to your health,” she says. “Relationships and a sense
of connection are as much a part of our health as playing
pickleball or eating salads.”
It can be especially challenging to sustain friendships
through your 80s and 90s, as many old friends start to
pass away. Bibi Elvers found herself in that situation in her
late 70s; now she’s 91, and many of her recent friendships
began at the Older Adult Centers run by Greenwich House
in New York City, where she regularly eats lunch and takes
classes in French, jewelry making and comedy. “I’ve outlived some of my old friends,” says Elvers. “But now I have
new friends from comedy class who I never would have
crossed paths with.” <BW>
T HANK YOU
to our Annual Disaster Giving
Program and Disaster Responder
Program members, whose generous
contributions are at work year-round
to provide help and hope to families
after devastating disasters — from
hurricanes and floods to home fires.
ANNUAL DISASTER GIVING PROGRAM MEMBERS
D I SASTE R R E S PON D E R PROG RAM M E M B E R S
7-Eleven Cares
Foundation
Choice Hotels
International
Harbor Freight Tools
Foundation, LLC
L’Oréal
Adobe
Cisco Foundation
Major League Baseball
The AES Corporation
CNA Insurance
Hewlett Packard
Enterprise Foundation
Ameriprise Financial
The Coca-Cola
Foundation
HP Foundation
Keurig Dr Pepper
Martin Marietta
DHL Supply Chain
Kimberly-Clark
Corporation
Mattress Firm
Pacific Life Foundation
McKesson Foundation
Prudential
MetLife Foundation
Raymond James
Assurant
AvalonBay
Communities, Inc.
Macy's, Inc.
Marathon Petroleum
Company LP
Northwestern Mutual
and the Northwestern
Mutual Foundation
Old Dominion
Freight Line
Organon
Avangrid Foundation
The DICK’S Sporting
Goods Foundation
Barclays
Discover
The Labcorp Charitable
Foundation
Big 5 Sporting Goods
Lenovo Foundation
The Middleby
Corporation
Reckitt
Dollar General
Build-A-Bear Foundation
Duke Energy
LHC Group
Neiman Marcus Group
CDW
Dutch Bros Foundation
LKQ
NextEra Energy, Inc.
Charles Schwab
Foundation
Equitable
Lockheed Martin
Corporation
Northrop Grumman
Foundation
Rodan + Fields
Prescription for Change
Project
FirstEnergy Corporation
Reynolds American Inc.
Ross Stores Foundation
Support Disaster Relief today at redcross.org
All corporate service marks used with permission. 422401-02 11/23
RTX
Ryder System, Inc.
Santander
Security Finance’s
Lending Hand Foundation
ServiceNow
Southwest Airlines
Stanley Black & Decker
Tata Consultancy
Services
U-Haul International
Yum! Brands
Zurich
Tailors
Blacksmiths
1
2
Crossing guards
& bridge tenders
1960
Rank
▼
Annual median income, 2023 dollars
1970
20
30
Furriers
Blacksmiths
Boardinghouse
keepers
$10k
40
Farmers
Housekeepers &
butlers
Product
promoters
Miscellaneous
motor vehicle
operators
Miscellaneous
motor vehicle
operators
Funeral
service
workers
Crossing
guards
Funeral
service
workers
Crossing
guards
2010
2000
Crossing
guards
Funeral
service
workers
2021
1k
10k
Miscellaneous
motor vehicle
operators
Number of workers over 65
1990
Household
cooks
70
Household
cooks
Household
launderers
1980
50
60
Americans may dream about being able to go off the clock when they
reach retirement age, but a good number simply can’t or won’t. We compiled data on the occupations with the highest share of workers older
than 65, going back seven decades. The job types held remarkably steady
over the years (farmers, tailors and clergy). A few faded out of the data
with time—blacksmiths, furriers and household launderers, for instance.
The data doesn’t tell us why people in some professions keep at it longer than others. But we know they’re largely low-paying jobs, which
means workers have likely struggled to put aside money for retirement.
�Dorothy Gambrell
Occupations with the highest share of workers over 65
3
DEEEEEEEEECEMBER 2023
WORK
100k
THE SILVER-TINGED
FORCE
LABOR
THE LOOOOOOOOONGEVITY ISSUE
56
Marshals &
constables
Milliners
Judges
Crossing
guards
& bridge
tenders
Piano tuners
& repairers
Farmers
Household
launderers
Household
cooks
THE LOOOOOOOOONGEVITY ISSUE
10
Boardinghouse
keepers
Guards
8
9
Railroad
conductors
Shoemakers
& repairers
Paper hangers
Locomotive
engineers
7
6
5
4
Shoe repairers
Elevator
operators
Farmers
Judges
Barbers
Crossing
guards
Household
cleaners &
servants
Shoe repairers
Optometrists
Barbers
Auctioneers
Household
cleaners &
servants
Judges
Clergy
Tax
preparers
Funeral
directors
Legislators
Farmers &
ranchers
Crossing
guards
DEEEEEEEEECEMBER 2023
Camera, watch & musical
instrument repairers
Judges
Funeral
directors
Tailors &
dressmakers
Barbers
Clergy
Tax
preparers
Farmers &
ranchers
Product
promoters
Miscellaneous
psychologists
Tailors &
dressmakers
Clinical & counseling
psychologists
Clergy
School
bus
monitors
School bus drivers
Tax
preparers
WORK
DATA: IPUMS, BLS, US CENSUS. OCCUPATION CATEGORIES ARE NOT CONSISTENT ACROSS DECADES. OCCUPATIONS WITH FEWER THAN 1,000 REPORTED WORKERS HAVE BEEN EXCLUDED
CREDITS CREDITS CREDITS
BEARI
DO N
WN G
ON
PARKINSON’S
Are scientists at last closing in on a drug to stop the progress of this disease?
By Robert Langreth Illustration by Kensuke Koike
59
60
THE LOOOOOOOOOONGEVITY ISSUE
R
andy Schekman, a cell biologist at the
University of California at Berkeley, won the
2013 Nobel Prize in medicine for his insights
into how yeast cells transport proteins to
where they’re needed. Some of that work
helped lead to biotech breakthroughs, including new ways to produce insulin and hepatitis vaccines.
Despite his brilliance, and his access to other brilliant scientists and doctors, Schekman sometimes felt
helpless after his wife, Nancy Walls, was diagnosed with
Parkinson’s disease in the late 1990s. Many of her symptoms were controlled by dopamine-boosting drugs, and
later a surgically implanted pacemakerlike device, but
that didn’t stop the disease from progressing. By the
time Schekman won the Nobel, Walls had developed
Parkinson’s-related dementia. In her final months she
was often in a zombielike state. She died in her sleep
in 2017 at age 68.
“There was nothing I could do to help her and nothing
I could do to prepare, because the disease progresses in
ways that are quite different,” Schekman recalls. “There
is no way to plan ahead.” So when a representative
from the family office of Google co-founder Sergey Brin
called on him shortly after his wife’s death to see if he
was interested in helping establish a vast program to find
the cause of Parkinson’s, it resonated. Now Schekman
and molecular biologist Ekemini Riley are helping lead
a new Brin-sponsored initiative called Aligning Science
Across Parkinson’s, or ASAP. Started quietly right before
the pandemic, it’s become one of the biggest funders of
Parkinson’s research in the world. The organization is
working hand in hand with the Michael J. Fox Foundation
for Parkinson’s Research, named after the Back to the
Future actor with the disease.
Brin has one of the most common Parkinson’s risk
mutations, in a gene called LRRK2, and he’s been a
heavy funder of research for years. He and his family foundation have donated almost $1.3 billion to the
cause and are the biggest donor to the Michael J. Fox
Foundation. “The family has been very good to us,”
says Fox in an interview at his office on New York’s
Upper East Side. Together the two groups are now putting more than $350 million a year into Parkinson’s
research, more than the National Institutes of Health,
with hundreds of millions of dollars more likely over
the next several years.
The goal is to develop disease-slowing therapies and
tests that can detect Parkinson’s before the development
of obvious symptoms, when the disease may be more easily treatable. ASAP can be thought of as the basic science
arm of the effort, building teams to help find genetic clues
and come up with new ideas for drugs and diagnostics.
The Fox Foundation proper is more focused on applied
research, devising the tools that companies can use in the
near to medium term to develop therapies.
It’s all badly needed. Parkinson’s is the second most
common neurodegenerative disease after Alzheimer’s.
Worldwide, 8.5 million people suffer from Parkinson’s,
and its prevalence has doubled in the past 25 years
as the population has aged. Most people first develop
symptoms after age 60. The disease causes cells that
produce dopamine to die, leading to stiffness, slowness,
tremors and a bewildering variety of other symptoms
including loss of smell, sleep disturbances, depression, psychosis and dementia. Exactly what triggers
Parkinson’s remains mysterious, though many clues
point to defects in cellular waste removal and debris
buildup inside delicate neurons.
US regulators gave full approval to the first diseaseslowing agent for Alzheimer’s, Eisai Co.’s Leqembi, in
July; approval of a second is expected in early 2024. No
such medicines exist for Parkinson’s. It’s been 60 years
since scientists discovered the effects of L-Dopa, the
symptom- alleviating drug featured in Awakenings,
a movie about patients with a rare Parkinson’s-like
encephalitis. But as effective as dopamine-boosting
drugs are in easing motor symptoms, they don’t arrest
or slow the death of brain cells, and they cause longterm side effects. The implanted device that Walls
PHOTOGRAPH BY CAYCE CLIFFORD FOR BLOOMBERG BUSINESSWEEK
SCHEKMAN AND
RILEY, LEADERS OF
ALIGNING SCIENCE
ACROSS PARKINSON’S
PARKINSON’S-SLOWING AGENTS: WHERE THEY STAND
Phase of trials
Company
Molecular target
Phase II (initial efficacy)
Biogen/Denali
LRRK2
Roche
Alpha-synuclein
UCB/Novartis
Alpha-synuclein
Phase I (safety)
Neuron23
LRRK2
Preclinical
AbbVie
PINK1
FUNDING
61
I
n 1817 a British surgeon named James Parkinson
described six people with a strange slowmoving disease he called “the shaking palsy.”
It usually started with trembling in the hands
or feet, he noted in a 66-page essay, and progressed over years until patients had trouble walking,
speaking intelligibly, sleeping or even feeding themselves. Efforts to understand the disease proceeded in
fits and starts over the next century and a half. In the
1870s the French neurologist Jean-Martin Charcot refined
the description, noting that profound slowness was a central feature, and renamed it Parkinson’s disease. Over the
next 50 years, researchers showed that damage to a structure deep inside the brain called the substantia nigra is
what causes Parkinson’s.
It wasn’t until the late 1960s, after dopamine was
shown to be a neurotransmitter produced in that part
of the brain, that a highly effective therapy was discovered: levodopa, or L-Dopa. It and numerous other drugs
that boost or modulate dopamine levels have remained
the mainstay of therapy for decades. But none of these
treatments solve the central problem, says Dimitri Krainc,
a neurologist at Northwestern University: “You feel better
with L-Dopa, but your neurons are still dying.”
Fox was diagnosed in 1991, at the age of 29, and
founded his nonprofit in 2000. The Parkinson’s drug
development field had begun to stagnate, and Fox
wanted to do something aggressive about drug development. He picked an energetic former Goldman
THE LOOOOOOOOOONGEVITY ISSUE
received, an electrical deep-brain stimulator, provides
substantial relief but doesn’t slow neuronal death.
The alliance of a brainy tech mogul and a high
school dropout actor has already found new leads and
largely avoided the scientific infighting that’s plagued
the Alzheimer’s field. In April researchers at the Fox
Foundation, the University of Pennsylvania and elsewhere confirmed that a spinal fluid test can accurately
spot a toxic protein called alpha-synuclein, which builds
up inside the neurons of Parkinson’s patients; this
advance could pave the way for new tests to monitor disease progression at its earliest stages. In August, ASAPfunded researchers in Nigeria, the UK and the US found
a gene variant that increases risk of the disease 3.5-fold
in people of West African descent, in one of the first big
studies of the genetic risk of Parkinson’s in that population. And in drug development, ASAP “has revolutionized the research,” says Dario Alessi, a biochemist at the
University of Dundee in Scotland who used to work on
cancer but now focuses exclusively on Parkinson’s. With
Fox Foundation funding, he’s designed laboratory tests
that drug companies use to search for treatments blocking
the LRRK2 protein that is overactive in people like Brin.
What Fox, Brin and Schekman don’t have is a
breakthrough treatment that can stop or even slow
Parkinson’s. A variety of companies, including Biogen,
Roche, Novartis and startup Neuron23, have begun
human trials with agents targeting potential molecular
causes of Parkinson’s. But most of these drugs are in
the early to middle stages of testing, and results won’t
start to roll in until the end of 2024 or later. At age 62,
Fox has lived with the ailment for half his life, and his
disease is progressing: He falls more often—including an
onstage fall at a fan expo in June—and has uncontrolled
movements from years of taking dopamine-producing
drugs. Brin recently turned 50 and, like millions of others with Parkinson’s risk mutations, faces a substantial
likelihood of developing symptoms in the coming years.
DEEEEEEEEEEMBER 2023
None of the current treatments
solve the central problem.
“You feel better with L-Dopa, but
your neurons are still dying”
advisory board to find ways to share resources to push
the research ahead.
The Fox Foundation has spread its bets widely. In
2010 it funded Neuropore Therapies Inc. to research
a drug targeting alpha-synuclein. That helped lead to a
compound now in Phase II trials at Belgian drugmaker
UCB SA and its partner Novartis AG. It also funded early
research at the University of California at San Francisco
that paved the way for a drug candidate against a third
Parkinson’s risk protein, called PINK1. In October, AbbVie
Inc. acquired the biotech company based on the UCSF
technology for $110 million. It could lead to the first
human trials for a drug targeting this protein.
I
n 2017, at a dinner with Fox and a group of Fox
Foundation donors, Brin told attendees that he
never expected to be working with the actor who
played Marty McFly, but he was impressed by the
quality of his foundation’s work. “Many other disease
categories would love to have an equivalent organization,” he said.
By that point, Brin’s family foundation was quietly
planning for a massive expansion of his Parkinson’s
efforts. In 2015 it had started working with the Milken
Institute Center for Strategic Philanthropy to identify gaps in research. Riley, who was then at the Milken
Institute, set up a series of meetings with top neuroscience researchers to determine the major deficiencies
that could be addressed if money were no object. “We’d
gotten the signal from the foundation that they were really
interested in doing something big,” Riley says. The assignment was “if you wanted to increase it and do something
bigger, what would you do?”
Around that time, Schekman started talking with
George Pavlov, a former venture capitalist who heads
Brin’s family office. Pavlov had heard about Walls’ diagnosis and wanted his advice on how one might deploy significant resources to move the science forward, Schekman
says. By that point, Walls’ dementia was advanced. She
would sometimes open her mouth to talk and not say a
word, having already lost the thought. She didn’t know
who the president was. On the plane ride home from the
2013 Nobel Prize ceremony, she had forgotten the reason for the trip.
A few months after Walls’ death, Pavlov invited
Schekman to chair a planning committee for Brin’s new
initiative, held during a big annual gathering of brain scientists. “I came away from that meeting thinking, ‘I have to
do this, whatever is involved,’ ” Schekman says. He and
PHOTOGRAPH BY VICTOR LLORENTE FOR BLOOMBERG BUSINESSWEEK
FUNDING
DEEEEEEEEEEMBER 2023
THE LOOOOOOOOOONGEVITY ISSUE
62
Sachs Group Inc. executive with limited nonprofit
experience, Deborah Brooks, to run the organization.
Fox and Brooks say it was an advantage to come into
the field without any biases or preconceived notions
about what might work. “I am an expert in frigging
Parkinson’s,” Fox says. “I have had it for 30 years. You can
be a Nobel Prize winner, and I can tell you stuff you don’t
know.” In his office, an honorary Academy Award given
to him for his charity work faces a giant black-and-white
print of him and the late boxer Muhammad Ali, who suffered for years from Parkinson’s.
His sense from the beginning, Fox says, was that “the
science was ahead of the money.” His foundation aimed
to give out grants faster and with less paperwork than
government funders while forcing scientists, who can be
highly competitive, to share data. It focused on blue-sky
research but also funded applied science that could lead
to drugs and diagnostics, including eventually providing
money directly to companies. Fox says his instructions
at the first board meeting were “I would like you to help
me go out of business.”
Well into the 1990s, Parkinson’s researchers remained
focused on environmental causes and, in particular, pesticides, says John Hardy, a geneticist at University College
London. “Everybody was taught that Parkinson’s was
not a genetic disease,” he says. That started to change
in 1997, when researchers at the National Institutes of
Health found the first genetic link to Parkinson’s, a rare
mutation in the alpha-synuclein gene. Since then, around
15 other Parkinson’s-promoting gene mutations have
been found. Although most Parkinson’s patients don’t
have these mutations, they still provide drug hunters
important clues to the molecular causes of the disease.
In 2004, Brooks heard through a contact that Eugenia
Brin, Sergey’s mother, had Parkinson’s. Through former Intel Corp. Chief Executive Officer Andrew Grove,
a Parkinson’s sufferer and an early adviser to the Fox
Foundation, Brooks was able to set up an introductory
dinner with Sergey Brin and Grove, leading to Brin’s first
large donation in early 2005. Brin “really wants to see this
happen,” Fox says. “He is exciting to work with because
you’ll literally tell him something and he’ll go, ‘Let’s do it.’ ”
Around this time, researchers at the NIH and elsewhere
discovered LRRK2 mutations, found in roughly 2% to 4%
of cases. The mutations produced an overactive enzyme
that could, in theory, be blocked with a drug to reduce
their activity. It was the same class of enzyme that’s been
successfully targeted to create many cancer drugs.
In 2008, Brin revealed in a blog post that he had
G2019S, a common LRRK2 mutation, and that he’d gotten it from his mother. At a meeting that year at Google
headquarters, Brooks says, she proposed a Manhattan
Project to speed research into LRRK2 to help pave the
way for treatments. At the time researchers knew little
about what LRRK2 mutations do in the body or how they
might contribute to Parkinson’s risk. Within the next few
years, numerous drug companies started researching
LRRK2. By 2011 the Fox Foundation, supported by Brin,
was funding 30 teams of academic scientists to understand what the mutations did. It also created an industry
CREDITS CREDITS CREDITS
FOX IN HIS
NEW YORK OFFICE
THE LOOOOOOOOOONGEVITY ISSUE
63
DEEEEEEEEEEMBER 2023
FUNDING
64
BROOKS, CEO OF
THE MICHAEL J. FOX
FOUNDATION
the multiple risk factors for the disease. A third team is
exploring whether Parkinson’s starts in odor-sensing
neurons before spreading to other parts of the brain. For
many patients, including Schekman’s late wife, a poor
sense of smell is the first symptom.
“The idea is to have lots of shots on goal” and not
get fixated on any one therapeutic strategy, Schekman
says. He contrasts ASAP’s broad approach with the
Alzheimer’s field, which, despite its recent success at creating disease-slowing drugs, has often been criticized for
focusing too heavily on one cause of the disease, amyloid
plaques. In Schekman’s view, that narrow approach has
diverted attention away from alternative avenues for
developing treatments, something he doesn’t want to
see happen with Parkinson’s research.
The odds that the first generation of gene-targeted
Parkinson’s drugs will succeed in trials are probably low.
With Alzheimer’s it took more than 20 years of failed drug
trials until the first big success in 2022. Parkinson’s progresses slowly, with effective symptom-masking drugs,
making testing potential disease-slowing agents in people a particularly long and difficult endeavor.
Over the years, at least a dozen drugs attempting to
slow Parkinson’s have failed in trials. In 2020 a Roche
Holding AG antibody against alpha-synuclein generated
mixed results in a Phase II trial, missing its main efficacy
goal; the company is now running a second big trial. In
February 2021, Biogen Inc. canceled research into its own
alpha-synuclein antibody after a Phase II trial showed no
benefit. The same month, Sanofi said its experimental
drug venglustat failed to slow Parkinson’s in a Phase II
trial of people with a specific genetic form of the disease.
The many uncertainties may be making some drug
executives hesitate before moving prototype drugs into
costly human trials—a reality that Brin’s billions of dollars can’t easily counteract. “A lot of them are sitting on
the fence,” Alessi says. “They have been burnt before,
so maybe their strategy is to wait and see what happens
before they decide what to do.”
In the case of drugs that aim at LRRK2 mutations, several of the companies that started researching them years
ago have not moved into human trials. GSK Plc worked on
LRRK2 drugs for at least six years, with early funding from
the Fox Foundation, and in 2018 it said the program had
the potential to move into human trials. Since then, the
company has made a business decision to focus on other
disease areas, according to a spokesperson. And while
Merck & Co. and Eli Lilly & Co. are looking into LRRK2,
neither has started human efficacy trials.
Some patient advocates worry whether drugs against
PHOTOGRAPH BY VICTOR LLORENTE FOR BLOOMBERG BUSINESSWEEK
FUNDING
DEEEEEEEEEEMBER 2023
Riley started working closely together to develop the
program that became ASAP. It was introduced in October
2019, with Riley as the day-to-day leader and Schekman as
the head of the scientific advisory board. It isn’t a separate
charity but funds and administers its programs through
the Fox Foundation. Schekman maintains his lab at UC
Berkeley, which is working on Parkinson’s. On a bulletin
board in his office, he’s tacked a faded snapshot of his wife
before she was sick.
A cornerstone of ASAP is a $290 million collaborative
research network that funds 35 teams from normally competitive labs to get a handle on numerous potential causes
of the disease. Schekman has long been frustrated with
incentives in academia that can discourage collaboration and data sharing between labs. “The way industry
works, it is a team effort,” he says. “In academic science,
the reward structure favors the individual.” To counteract this tendency, Schekman and Riley require that teams
include scientists from multiple institutions and assign a
doctoral-level project manager to each team to make sure
those institutions continue to work together.
Alessi, the researcher in Scotland, is working with
Stanford University on one team to figure out how
LRRK2 mutations damage neurons. Another team, led by
Memorial Sloan Kettering Cancer Center stem cell biologist Lorenz Studer, is using stem cells to better understand
DEEEEEEEEEEMBER 2023
65
we have known that synuclein was a key pathology in
Parkinson’s disease,” says Kenneth Marek, a neurologist
at the Institute for Neurodegenerative Disorders and a
senior author on the study. “Now we can measure it in
life and don’t have to wait for someone to die.”
Fox hopes that advances like this can eventually help
to treat people when more neurons are intact and there’s
still a chance of preserving them. Toward this end, the
Fox Foundation plans to soon start working with multiple drug companies on trials aimed at disease prevention. Such trials are likely to be long and expensive, and
it’s not clear how many drug companies would be willing
to do it on their own. The foundation plans to take some
of the risk off the table by partially subsidizing the trials
and providing a giant cohort of at-risk people who’ve
already agreed to be in a study. It says it’s received letters of interest from numerous drug companies, though
no deal has been finalized.
Fox says he’s not expecting anything his foundation is
doing will generate cures for himself. He’s too far along
in the progression of the disease for many treatment trials. “I don’t think about that,” he says. Nonetheless he
sometimes gets impatient that progress can’t happen
faster. Schekman says his own goal is to generate lots of
new leads for drugs and devices over the next five years.
“If we could find a drug that was designed to mitigate
or relieve the progression in one genetic, one familial
form of Parkinson’s,” he says, “that would be a tremendous victory.” <BW>
THE LOOOOOOOOOONGEVITY ISSUE
any of the genetic targets will make much of a difference
in people who already have symptoms. Benjamin Stecher
of Toronto was diagnosed with Parkinson’s at 29 years
old, the same age as Fox when he received his diagnosis. He’s now 39 and says he’s grown skeptical of the Fox
Foundation’s focus. In particular he’s not convinced the
gene-based approach to developing drugs will pay off.
Although Stecher has one of the Parkinson’s-promoting
mutations that drugmakers are targeting, called GBA1, it’s
far from clear that a drug that counteracts it could make a
difference at his stage in the disease. “I don’t think going
after the genetics of the disease will translate into treatments for patients like me, ever,” he says. In his view the
foundation should put more emphasis on developing digital tools that could customize symptomatic treatments for
existing patients and do more work on improving existing electrical stimulation therapies.
By the time Stecher, Fox and Eugenia Brin were diagnosed with Parkinson’s, they likely had already lost about
50% of their dopamine-producing brain cells. That’s the
best estimate doctors have, based on autopsy studies of
patients who died at various stages of the disease. In a living patient, it’s hard to tell for sure, because there are few
tests that can peer inside the brain to determine how the
pathology is progressing in real time.
In Alzheimer’s, the advent of specialized brain scans
to detect buildup of amyloid has aided the testing of
disease-slowing drugs. A way to measure Parkinson’s
pathology early in the course of the disease with a scan
or blood test could undoubtedly speed the testing of
disease-slowing drugs, but Parkinson’s still lacks a way
to quantitatively measure alpha-synuclein pathology in
living patients, making drug studies much harder.
But researchers are getting closer. The recent study
from the University of Pennsylvania and Fox Foundation,
reported in Lancet Neurology, found that a spinal fluid
test can accurately detect alpha-synuclein pathology
in about 90% of Parkinson’s patients. (The test is available, but insurance may not cover it.) “For 100 years,
FUNDING
“Now we can measure it in
life and don’t have to wait for
someone to die”
HOSPICE
DEEEEEEEEEEECEMBER 2023
THE LOOOOOOOOOOONGEVITY ISSUE
66
CAN AI
HELP YOU DIE?
Doctors in New Jersey are experimenting
with software to prompt discussions with patients
about palliative or hospice care
By Cailley LaPara Illustration by Lennard Kok
D
octors
can be slow
to talk about the
end of the traditional medical
road. When they’ve been trying to manage a life-threatening illness or keep a terminal
patient alive, bringing up palliative or hospice care can feel like
giving up. But these options can radically improve quality of life, or
the end of life, when traditional medicine hasn’t helped enough—
if patients and their doctors figure it out in time. Some providers just don’t recognize when the end is near until it’s very near,
says Mihir Kamdar, a doctor at Massachusetts General Hospital
in Boston who heads clinical health at a palliative-care startup
called Tuesday Health. “When someone is actively declining, you
can see it, but being able to predict before that happens is hard.”
Can artificial intelligence software do a better job than humans
of picking that moment? That’s the idea behind Serious Illness
Care Connect, a software tool that about 150 doctors are testing in a pilot program in New Jersey’s largest health-care network, Hackensack Meridian Health. Developed by an in-house
team of data scientists and hospice providers, SICC is a statistical model trained on a year’s worth of anonymized Hackensack
Meridian patient data. It gets built into the software doctors use
to review and update patient records. The tool calculates the likelihood that a patient will die within six months, a common medical benchmark for these kinds of decisions.
If the chance of death in that window is 70% or higher, SICC
recommends an evaluation for end-of-life hospice care. It’s a cold
calculation, but one that doctors hope can help bring greater relief
to suffering patients: Hospice often includes psychological and
spiritual services as well as physical care. If the chance is between
30% and 69%, the software suggests a conversation about palliative care, a holistic approach to living with chronic illness.
The team behind SICC says it doesn’t yet have meaningful
data on the software’s performance; the current test phase began
in June. Other forms of predictive technology in medicine have
run into challenges: Insurers UnitedHealth, Cigna and Humana
are facing lawsuits alleging that they used algorithms to wrongfully deny coverage. (In response, UnitedHealth and Humana have
said people are always involved in coverage denials; Cigna has
said the purpose of its AI tool has been mischaracterized.) The
Hackensack Meridian team stresses that the tool isn’t making
decisions. “Think of this as a ‘check engine’ light,” says Lauren
Koniaris, the chief medical informatics officer at Hackensack
Meridian. “It’s a gentle nudge to help us take the best care of our
patients.” A larger pilot phase is planned for early 2024.
In the meantime, the doctors and developers are encouraged
to be mindful of the bias that’s regularly, often unwittingly, built into
AI algorithms. The tools are only as good as the data that goes
into them, so developers aim to use data from a diverse patient
population to avoid skewing results toward a certain race, age,
gender or other characteristic. Disparities are already abundant
in palliative care, study after study has revealed. In 2020, 48% of
Medicare patients who died were enrolled in hospice at the time
of death, according to a recent report from the National Hospice
and Palliative Care Organization. Broken down by race, however,
more than half of White patients used hospice whereas only about
a third of Black and Hispanic patients did.
Hackensack Meridian’s senior vice president and chief data
and analytics officer, Sameer Sethi, says the development team’s
analysis of SICC showed the model had no specific biases as of
May 2023. But they continue to test whether the software disproportionately recommends a particular outcome to particular
populations, Sethi says.
If the industry’s engineers can navigate these challenges,
they’ll find plenty of customers among America’s overworked doctors. Kamdar says he expects to see a wide range of AI products join the field in the next several years, such as tools that
allow patients to more easily track their symptoms. As uncomfortable as it can be for doctors and patients to talk about end-oflife options, putting off the conversation is even worse. Digesting
data to deliver a gentle nudge could be a good spot for AI in
health care. But only humans can ensure equitable outcomes. <BW>
Data that’s
made for more.
What could you do if your data was working for you
and not against you? With Bloomberg delivering
enterprise data directly to your systems, you get
easy access to the information you want, optimized
for higher-level analysis, and experts committed to
helping you do more with data.
Think bigger with Bloomberg enterprise data.
Learn more.
AN OPERATING ROOM WHERE PROTECTANTS ARE INJECTED INTO BODIES TO PREVENT FREEZING THAT MIGHT DAMAGE ORGANS DURING CRYOPRESERVATION
For $200,000 you can have your body cryogenically preserved after death.
The question is: To what end?
Photographs and text by Alastair Philip Wiper
CREDITS CREDITS CREDITS
ETERNAL
A POST-DEATH COOLING PROCEDURE IS DEMONSTRATED USING A DUMMY
LIF
?
E
CREDITS CREDITS CREDITS
N
ELI
OUT THERE
DEEEEEEEEEEEECEMBER 2023
THE LOOOOOOOOOOOONGEVITY ISSUE
70
ALCOR’S PATIENT-CARE BAY, WHERE BODIES ARE CRYOPRESERVED AT -196C (-321F) IN SPECIALIZED CONTAINERS CALLED DEWARS
tour of Alcor Life Extension Foundation’s
headquarters in Scottsdale, Arizona,
includes some unique sights. The nonprofit has more than 200 human bodies
or heads—and a few beloved pets—in cryogenic preservation on-site.
Founded in 1972 by Fred and Linda
Chamberlain, Alcor is dedicated to cryonics research
and education and has about 1,500 members planning
on some form of cryogenic preservation. While they’re
still living, members wear medical alert bracelets that
instruct hospitals and doctors to contact the organization in the event of a life-threatening emergency. A team
is on standby to rush the body of any member who dies
to Alcor’s facility. There, bodily fluids are replaced with
special solutions that won’t turn to ice during the next
step in the preservation process—cooling the cadaver to
-196C (-321F).
A
The operation required to process and protect a body
upon arrival is extensive, and the chemicals used for vitrification are unique, accounting for the hefty price tag:
$200,000 for the whole body or $80,000 for just the head,
plus monthly membership fees of up to $100. (Most members pay by designating Alcor as the beneficiary of their life
insurance policies.) User fees cover about 40% of the cost,
with the rest coming from donations.
James Arrowood, co-chief executive officer of Alcor,
describes cryogenics as a serious scientific undertaking,
deemphasizing the more outré associations it has in the
public imagination as just a way to cheat death. He
OUT THERE
THE LOOOOOOOOOOOONGEVITY ISSUE
DEEEEEEEEEEEECEMBER 2023
ARROWOOD
71
THE LOOOOOOOOOOOONGEVITY ISSUE
DEEEEEEEEEEEECEMBER 2023
72
A STORAGE POD THAT CAN HOLD 10 CRYOPRESERVED HEADS
OUT THERE
THE LOOOOOOOOOOOONGEVITY ISSUE
A KIT USED BY ALCOR RESPONDERS
DEEEEEEEEEEEECEMBER 2023
73
OUT THERE
OUT THERE
DEEEEEEEEEEEECEMBER 2023
THE LOOOOOOOOOOOONGEVITY ISSUE
74
INSIDE THE PATIENT-CARE BAY, THE DEWARS MUST BE REGULARLY TOPPED OFF WITH LIQUID NITROGEN BUT DON’T REQUIRE ELECTRICITY
THE LOOOOOOOOOOOONGEVITY ISSUE
DEEEEEEEEEEEECEMBER 2023
75
OUT THERE
OUT THERE
DEEEEEEEEEEEECEMBER 2023
THE LOOOOOOOOOOOONGEVITY ISSUE
76
CLOCKWISE FROM TOP LEFT: ALCOR’S
SCOTTSDALE HEADQUARTERS; A CARD
CONTAINING INFORMATION ABOUT THE
MEMBER’S WISHES UPON DEATH;
BODIES ARE PUT IN SLEEPING BAGS
AND PLACED IN DEWARS HEADFIRST
sees scientific research as the heart
of Alcor’s mission. “I know what happens if I choose cremation,” Arrowood
says. “I know what happens if I choose
burial. I also know what the loss is
to the science.” He gives the example of Albert Einstein’s brain, which
was removed for study but was cut
into pieces because there was no way
to preserve and examine it in a nondestructive way. If there had been,
Arrowood says, we could have learned
more about the unique nature of the
scientist’s genius. “Einstein’s brain is
all over the world in little chunks,”
he says. “And you can never get that
data back.”
Alcor has accumulated a repository of data on organ preservation
and decay that spans more than five
decades. It has in storage the brain of
someone born in the 1880s and someone born in the 2000s. Much of what
it was doing in its early years was aspirational and felt like science fiction,
Arrowood acknowledges, but he adds
that cryogenics isn’t as weird as it’s
DEEEEEEEEEEEECEMBER 2023
OUT THERE
made out to be. With in vitro fertilization, “embryos are
frozen indefinitely,” he says, “and they ultimately result in
a living being.”
As technology has progressed, advances such as
improved preservation of individual organs have become
viable goals. Arrowood cites kidney donation as an area in
which Alcor might be able to make a difference—notably
by preserving kidneys long enough after a donor’s death to
line up a match and arrange for surgery. “That is a solvable
problem,” he says. “It’s not fiction.”
Arrowood also sees potential for Alcor to contribute to
scientific knowledge about what happens to bodies after
death and to serve as a kind of seed bank, helping preserve
species that are near extinction.
Naturally, he’s planning to be cryopreserved himself. “Have you seen a cremation? They’re awful! Or
burial? You get eaten by worms! I’ve never liked worms,”
he says. “I am choosing to be a part of a supercool
science experiment.”
THE LOOOOOOOOOOOONGEVITY ISSUE
CLOCKWISE FROM LEFT: A REFRIGERATOR
FULL OF M22, THE SOLUTION USED
IN VITRIFICATION, CURRENTLY THE
PREFERRED METHOD FOR CRYOPRESERVATION;
AN ALCOR MEMBERSHIP BRACELET;
PHOTOS OF PEOPLE WHOSE BODIES ARE
BEING PRESERVED AT ALCOR
77
OUT THERE
DEEEEEEEEEEEECEMBER 2023
THE LOOOOOOOOOOOONGEVITY ISSUE
78
R. MICHAEL PERRY, WHO’S WORKED FOR THE ORGANIZATION SINCE 1989, MONITORS ALCOR’S FACILITIES
OUT THERE
DEEEEEEEEEEEECEMBER 2023
THE LOOOOOOOOOOOONGEVITY ISSUE
THE CRYOGENIC STORAGE DEWAR THAT HELD THE BODY OF R. JAMES BEDFORD, THE FIRST PERSON TO BE CRYOPRESERVED;
AFTER MORE THAN 20 YEARS, HIS BODY WAS MOVED TO A NEWER CONTAINER
79
THE LOOOOOOOOOOOOONGEVITY ISSUE
80
DEEEEEEEEEEEEECEMBER 2023
The average American business closes shop after about
21 years. (Of course, the back half of the bell curve never
reaches drinking age.) Some businesses, though, last longer—a
lot longer. Take Kongo Gumi, a Japanese construction company
founded in 578 A.D., or Santa Maria Novella, an Italian pharmacy
that’s been perfuming the elite since Michelangelo was decorating ceilings. Here are some longevity lessons from businesses
that know something about survival. �Angela Serratore
BROOKS BROTHERS, EST. 1818
Lesson: Change—but not too much
Founded as a small clothing manufacturer
and shop in Lower Manhattan, Brooks
Brothers has been supplying starched
shirts and blue blazers for more than
200 years. When Ken Ohashi took over
the company in late 2020, it was a strange
time for a brand that depends on more
formal wear. Brooks Brothers pivoted,
and casual wear such as oversize striped
rugby shirts now account for 40% of sales.
“Our core customer loves our sweatpants,” Ohashi says, “because you can
get them monogrammed.”
THE OLDE BELL, EST. 1135
Lesson: Furniture changes, but service
shouldn’t
Once upon a time, you might pull into
the Olde Bell hotel, about 35 miles outside London, expecting to get a pint of ale
and a hunk of bread to dip in your stew
before you fell asleep on a horsehair bed.
Since then, the Olde Bell has expanded to
include more guest quarters and a nuclear
fallout shelter-turned-wine cellar, but the
idea that every traveler deserves a place
to rest and a pint of ale remains the same,
says sales manager Debi Hayes—“except
we’ve got comfier mattresses now!”
SANTA MARIA NOVELLA, EST. 1612
(PHARMACY FROM 1542)
Lesson: Signature products are signature
products for a reason
For Gian Luca Perris, chief executive
officer and “nose” of Officina ProfumoFarmaceutica di Santa Maria Novella, the
brand’s most enduring fragrance is inextricably linked to its most famous patron:
Catherine de’ Medici. Acqua della Regina,
with top notes of petitgrain and a base of
musk, is still one of Santa Maria Novella’s
bestselling products, a chance for today’s
shoppers to capture a little bit of long-ago
glamour and romance.
KONGO GUMI CO., EST. 578
Lesson: Find a niche and don’t let go
Until it became a subsidiary of Takamatsu
Construction Group in 2006, Kongo Gumi
was the world’s oldest continuously operating company. Even now it still does
things the really, really old-fashioned
way. Its specialty is the restoration of
Buddhist temples and other historic buildings, where workers were sometimes set
against one another, competing to see
which craftsperson demonstrated the
most skill in working with the timber and
clay traditionally used to build temples.
CONSOLIDATED EDISON, EST. 1823
(AS THE NEW YORK GAS LIGHT CO.)
Lesson: Location, location, location
ConEd, energy provider to New York
City and many of its surrounding counties, is the oldest continuously operating
company listed on the New York Stock
Exchange. It even predates Thomas
Edison himself—when he was born in 1847,
the company that would bear his name
was known as the New York Gas Light Co.
By the mid-1920s, ConEd wiped out the
competition, becoming the sole source of
electric light in a city known for it.
ST. PETER STIFTSKULINARIUM,
EST. C. 803
Lesson: Don’t be afraid to mix it up
St. Peter Stiftskulinarium—long known for
its wine collection—has been delighting
diners in Salzburg, Austria, for more than
1,200 years. Nora Wunderwald, a spokesperson for St. Peter, says patrons such as
Mozart, Faust and Karl Lagerfeld would go
for the food as well as drink. The restaurant makes it a point to diversify the menu.
Recent offerings have included confit fillet
of char, artichoke Wellington and an innovation Charlemagne and his compatriots
would surely have marveled at: brunch.
Bloomberg Businessweek (USPS 080 900) December 25, 2023 (ISSN 0007-7135) H Issue no. 4809 Published weekly, except one week in February, April, May, June, July, August, September, October and November by Bloomberg
L.P. Periodicals postage paid at New York, N.Y., and at additional mailing offices. Executive, Editorial, Circulation, and Advertising Offices: Bloomberg Businessweek, 731 Lexington Avenue, New York, NY 10022. POSTMASTER: Send
address changes to Bloomberg Businessweek, P.O. Box 37528, Boone, IA 50037-0528. Canada Post Publication Mail Agreement Number 41989020. Return undeliverable Canadian addresses to DHL Global Mail, 355 Admiral Blvd., Unit 4,
Mississauga, ON L5T 2N1. Email: contactus@bloombergsupport.com. QST#1008327064. Registered for GST as Bloomberg L.P. GST #12829 9898 RT0001. Copyright 2023 Bloomberg L.P. All rights reserved. Title registered in the
U.S. Patent Office. Single Copy Sales: Call 800-635-1200 or email: bwkcustserv@cdsfulfillment.com. Educational Permissions: Copyright Clearance Center at info@copyright.com. Printed in the U.S.A. CPPAP NUMBER 0414N68830
TIME-TESTED
LONGEST-RUN
ESSES
IN
BUS
Matt
Levine
knows
money.
Get Money Stuff from
Bloomberg Opinion’s
finance expert.
Sign up
Columnist,
Bloomberg Opinion