RESEARCHING
AGE-RELATED WEIGHT GAIN
A PEPT ID E SCI ENCE S EDU C ATIONAL INS IGH T
CONT E N TS
01
WHAT IS SOMATOPAUSE?............ 5
02
THE ROLE OF PEPTIDES IN WEIGHT GAIN........ 9
WHAT ARE PEPTIDES?..................... 10
GROWTH HORMONE RESEARCH
AND ENERGY BALANCE.....................................11
MITOCHONDRIAL RESEARCH
AND METABOLISM................................ 16
HORMONE RESEARCH AND HUNGER............ 18
03
CONCLUSION............ 23
04
RESOURCES............ 25
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE
ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
THE PRODUCTS WE OFFER ARE NOT INTENDED FOR HUMAN USE DIRECTLY. THEY ARE INTENDED FOR IN-VITRO AND PRE-CLINICAL
RESEARCH PURPOSES ONLY. THESE PRODUCTS ARE NOT MEDICINES OR DRUGS AND HAVE NOT BEEN APPROVED BY THE FDA TO
PREVENT, TREAT OR CURE ANY MEDICAL CONDITION, AILMENT OR DISEASE.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
2
INTRO
RESEARCHING
AGE-RELATED WEIGHT GAIN
Hormones control almost everything in our bodies,
from growth to metabolism to how fast our hair
grows. As we age, levels of hormones change, altering
the way our bodies work. Most everyone has heard
of menopause, the decline in estrogen that occurs in
women as they age. Many people have also heard of
low T (andropause), which is the decline of testosterone
in men with age. There is another hormone change
that many people have not heard of, however, called
somatopause. Scientists are paying a lot of attention
to somatopause because research shows that it has
dramatic effects on weight gain, fat mass, muscle mass,
bone strength, heart health, mood, and more.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
3
01
WHAT IS
SOMATOPAUSE?
01
WHAT IS
SOMATOPAUSE?
Just like testosterone and estrogen, growth hormone
(GH) levels decline with age. Lower levels of GH make
it harder to build muscle and burn fat. This decline in
growth hormone with age is known as somatopause.
Research
indicates
that
somatopause is one reason
why we get fatter as we
age. It is also why exercise
becomes less effective and
contributes to a decline in
physical function declines
Pattern of GH changes with age.
Levels peak at age 20 and then begin to
steadily decline around age 30.
as we age as well. It can
Source: National Library of Medicine
fat accumulation, increased
lead to frailty, abdominal
triglyceride and cholesterol levels, increased risk
of heart disease, and even deterioration of mental
function. Animal studies show that growth hormone
levels decline by about 15%, per decade, starting at
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
5
level changes, is the major reason that we all gain
cha pt er o ne
the age of 30. This, combined with other hormone
1-2 pounds every year from age twenty to about age
sixty[1]. Unfortunately, most of that weight gain is in
the form of fat.
Age-Related Weight Gain and Body Composition
Somatopause is a major factor contributing to agerelated changes in “body composition” or the ratio of
lean body mass (i.e. muscle and bone) to fat. However,
it isn’t the only factor that affects body composition.
Changes in mitochondrial function and the hormones
that control hunger contribute as well. Less energetic
mitochondria burn less energy at rest, lowering baseline
metabolism. At the same time, changes in certain gut
and brain chemicals can affect our appetite and even
the types of food we crave.
Fighting against these changes is difficult because
it means fighting an uphill battle against our very
biology. Lower levels of GH make us less responsive
to exercise and decrease our energy levels. Changes
in mitochondria mean we burn fewer calories at rest.
Alterations in neurotransmitters mean we seek out
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
6
cha pt er t w o
“RESEAR C H HAS S HO W N T H A T
PEPTI D ES C AN HEL P R EV E R SE
A GE-RELA TED W EIGHT GAIN A N D
M AYBE EV EN EX T END L I F E ”
foods that are less healthy
and more fattening. Simply
put, we have to work
harder than ever before to maintain a healthy body
weight as we age. Unfortunately, this often means we
fall into a vicious cycle of ever-increasing weight gain.
It isn’t all bad news though.
The Good News About Age-Related Weight Gain
Science is uncovering new ways to combat age-related
weight gain by restoring growth hormone to more
youthful levels, regulating fat burning in mitochondria,
and altering feelings of hunger and fullness (satiety).
Research in animals has shown that peptides can help
reverse age-related weight gain and maybe even extend
life by resetting metabolism to more youthful level.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
7
02
THE ROLE OF
PEPTIDES IN WEIGHT GAIN
02
THE ROLE OF
PEPTIDES IN WEIGHT GAIN
Peptides are not new. Scientists have been investigating
their properties since the mid-1800s. Research in
the area was hampered, however, by the difficulty
of obtaining peptides. Until recently, most peptides
were either harvested from animals or collected
from cadavers. With the development of modern
synthetic biology, however, peptides can be produced
quickly, reliably, and affordably in a laboratory. The
result has been an explosion in peptide research in the
last fifty years.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
9
M O D E R N SY N T H E T I C BI OL O G Y ,
cha pt er t w o
“W I T H T H E D E V E L O P M E N T O F
H OW E V E R , P E P T I D E S C A N BE
P R OD U C E D Q U I C K L Y , R E L I A B LY ,
A N D A F F OR D A BL Y I N A
L A BO R A T O R Y . "
What Are Peptides?
Peptides are short proteins made up of tiny parts called
amino acids. Peptides are remarkable for their ability
to manifest ever more complex structures from these
simple building blocks. This gives peptides and proteins
an almost limitless set of properties, which explains
why they are critical in many aspects of biology.
One fundamental role of peptides is as signaling
molecules to help the body coordinate activities like
growth, immune function, energy balance, and more.
As we will see, this means that peptides, acting as
hormones, play fundamental roles in regulating
metabolism, weight, hunger, growth, sleep, and more.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
10
" IF WE TAKE IN MO R E ENE R G Y
Energy balance refers to
TH AN WE USE, O U R B O D IES S T O R E
how our body deals with
IT AS F AT AND GL YC O GE N. "
cha pt er t w o
Growth Hormone Research and Energy Balance
differences between the
energy we take in and the
energy we use in a given day. If we take in more energy
than we use, our bodies store it as fat and glycogen.
When we take in less energy than we need, our bodies
tap into those energy stores to meet demand. Peptides
regulate this energy balancing act and can tip the
scales toward or away from storage.
Growth hormone is a primary energy balance hormone.
High levels of GH favor muscle and bone growth while
preventing fat storage. As we age, GH levels fall and the
balance shift. We start to gain fat and lose muscle While
it is possible to supplement directly with GH, research
shows that this approach has too many serious side
effects to be useful. Animal research suggests that the
better approach is to stimulate the body to make more
GH naturally. Some peptides, like sermorelin, GHRP-6,
CJC-1295, and others do just that. These peptides are
derived from the molecules that control GH production
in the pituitary gland.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
11
cha pt er t w o
The Growth Hormone Cycle
Author: OpenStax College
Source: Anatomy & Physiology,
Connexions Web site.
Compounds that Show Promise
Before we examine a few of the more exciting compounds
involving metabolism, let’s think forward to the exciting
breakthroughs on the horizon. Peptides can provide
the stimulus necessary to keep cells producing energy,
dividing, replicating themselves efficiently, as well as
efficiently disposing of degraded cellular matter. As we
better understand the ways peptides can be harnessed
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
12
cha pt er t w o
to optimize cellular function, we are also improving our
ability to synthesize these powerful compounds. The
original forms of commercially available insulin and
growth hormone were extracted from cadavers! With
modern technology these peptides are now synthesized
and we are getting better at it quickly.
The likelihood is, the future of peptides is one where
they will be increasingly used to treat all forms of
metabolic disorder. Anything that interferes with highly
energetic and vibrant life is put on notice. Things like
cancer treatments, the maintenance of healthy organs,
muscles, and bones will be at the top of that list. This
will be a general extension of youthful appearance
and cellular health. Imagine a world where 60 and 70
year olds still have the hair, skin, and bodies they did
in their 30s. This is not even an extreme example of
what is achievable the more we learn how to positively
influence cellular health with these compounds. More
important are the things that will be addressed both
directly and by second order preventative action. Yes
healthy cells resist anomaly, but peptides are also
showing massive success directly effecting the signaling
pathways that may allow us to enhance our immune
and regenerative properties far beyond anything we
are capable of today.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
13
cha pt er t w o
Research with Growth Hormone Secretagogues
(Growth Hormone Mimics)
Most of the research into growth hormone has
studied the class of peptides known as growth
hormone secretagogues. These peptides boost levels
of GH secretion from the anterior pituitary gland by
simulating the effects of growth hormone releasing
hormone (GHRH). The benefits of this approach
are that it allows the body to maintain normal
patterns of GH secretion as well as normal feedback
control of GH production. Together, these reduce
the risks of side effects and overdose while making
administration simpler.
The growth hormone secretagogues can be broadly
divided into two categories. The first are growth
hormone releasing hormone analogues like sermorelin
and CJC-1295. These peptides cause a physiologic but
enhanced release of GH and have few if any side effects.
The second category are growth hormone secretagogue
receptor agonists that mimic the natural peptide
ghrelin. Peptides like GHRP-2, GHPR-6, hexarelin, and
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
14
represent some of the earliest peptides for weight loss
cha pt er t w o
ipamorelin fall into this category. These peptides
ever developed and tested. The ghrelin mimetics are
well known for their ability to cause dramatic increases
in GH levels.
Fragment 176-191 (Growth Hormone Analogue)
Fragment 176-191 is a small piece of the larger GH
protein. It works by mimicking
the effects of GH in the body and
by increasing the density of the
beta-3 adrenergic receptor that
controls how fast we burn fat.
Fragment 176-191 appears to
only affect fat tissue. Research
LEARN
MORE >>
in mice shows that only obese
mice lose weight while using this
peptide. Normal weight mice
simply maintain their body weight[2].
AOD9604 (Growth Hormone Analogue)
AOD9604 is derived from growth hormone and
specifically developed to maintain the lipolytic (fat
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
15
cha pt er t w o
burning) features of growth
hormone without retaining any
LEAo
R Nf
<< MORE
growth hormone’s other effects.
AOD9604 increases weight loss
3-fold compared to placebo. It
especially
affects
beta-3-
adrenergic receptor density on
white fat to increase rates of fat breakdown. AOD9604
has been shown to be one of the most effective peptides
for weight loss, with animal studies showing as much
as a 50% reduction in weight gain over just three-weeks
of administration[2].
Ipamorelin (Ghrelin Mimetic)
Ipamorelin
simulates
the
effects of ghrelin and causes
a natural GH release from
the
anterior
oL E fA R N
pituitary.
It
is
interesting for its weight loss
properties and its ability
MORE >>
t o
to stimulate bone growth.
Ipamorelin
is
undergoing
research as a potential treatment for osteoporosis and
other bone-loss conditions[3]–[5].
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
16
cha pt er t w o
Mitochondrial Research and Metabolism
Another place in which peptides have shown promise
is in the regulation of metabolic rate. Simply defined
as the rate at which we burn energy, metabolism is the
fundamental process that sustains life in an organism.
Disruptions of metabolism can lead to everything from
obesity to extreme weight loss, cancer, disorders of
“ MET AB O L IS M IS T H E
FUN D EMENT AL P R O C ES S T H A T
the immune system, and
can even accelerate the
process of aging itself.
SUS TAINS LI F E IN AN O R GANI SM ”
Most of the energy our
bodies use is produced in tiny compartments inside of
cells. These compartments, called mitochondria, are
where food energy is converted into energy that our
body can use. The faster mitochondria work, the higher
our metabolism is and the faster we “burn” calories.
Research shows that peptides can regulate the rate at
which mitochondria work, turning them up or down.
This can be used to fine-tune energy balance. Increasing
metabolism this way can especially help to burn fateven without exercising!
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
17
Ipamorelin is a highly selective growth hormone (GH)
cha pt er t w o
CJC-1295 + Ipamorelin
secretagogue[1]. By acting on the ghrelin/growth
hormone secretagogue receptor, ipamorelin improves
bone health, boosts muscle repair
and development, stimulates insulin
release, and improves bowel motility
and gastric function[3] [5] [19]–[21].
LEARN
MORE >>
CJC-1295 (without DAC aka Modified
GRF) causes GH release by stimulating
the
growth
hormone
positive
hormone
receptor.
benefits
on
It
releasing
is
bone
has
demonstrated
health,
lean
body
mass, insulin resistance, and muscle growth and
development[22]–[24]
Combining the two peptides may produce enhanced
effects by stimulating the growth hormone axis via two
different receptors. CJC-1295 will be produce both higher
peaks and higher troughs while preserving normal
growth hormone pulsatile secretion. Ipamorelin will
further augment those peaks. Together, the peptides
could lead to a higher set point for the normal ebb and
flow of natural GH release, resulting in improved lean
body mass, better muscle development, and overall
better metabolic function.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
18
Research Formula
cha pt er t w o
Longevity, Performance & Obesity
5-amino-1MQ is a small molecule that blocks the activity
of nicotinamide N-methyltransferase (NNMT). Blocking
NNMT increases NAD+ levels, improves metabolic rate,
and activates sirtuin-1 (SIRT1). SIRT1 is known as the
"longevity gene" because of its role in reducing the
risks of multiple diseases[10] [25]–[26].
NMN (Nicotinamide mononucleotide) is a unique form
of vitamin B3 that gets converted into Nicotinamide
Adenine Dinucleotide (NAD+). NAD+ declines with age
and is an essential coenzyme for energy production,
cellular repair, and the regulation of aging (via
sirtuins). NMN supports the synthesis of NAD+ and may
therefore decrease age-associated body weight gain,
improve energy metabolism and
glucose homeostasis, alter plasma
lipid profiles, enhance eye function,
and improve insulin control[27]–[30].
LEARN
<< MORE
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
19
cha pt er t w o
JBSNF-000088 inhibits NNMT activity, reduces MNA
levels, and drives insulin sensitization, glucose
modulation, and body weight reduction in animal
models of metabolic disease. In mice with high fat
diet (HFD)-induced obesity, JBSNF-000088 caused a
reduction in body weight and normalized glucose
tolerance to the level of lean control mice.
These three compounds primarily affect levels of NAD
(both directly and via decreased NNMT activity) and
increase the expression of GLUT-4 receptors. Together,
these effects improve cellular metabolism, enhance
weight loss, and improve glucose control. Additionally,
increased levels of NAD help stem cells to survive
and thrive, providing a pool of healthy cells that
can readily take the place of those that are worn or
damaged. This leads to improved tissue function and
decreased effects of aging. Activating sirtuin-1 (SIRT1),
the "longevity gene," can reduce the risks of diabetes,
obesity, metabolic syndrome, cardiovascular disease,
kidney disease, liver disease, and neurodegeneration.
By combining these three research compounds, it might
be possible to drastically alter energy metabolism for
the better while simultaneously boosting anti-aging,
anti-inflammatory, and anti-apoptosis activity in cells.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
20
MOTS-c is a very short peptide, even among peptides for
cha pt er t w o
MOTS-c (Mitochondrial/Nuclear Gene Regulator)
weight loss, which allows it get into mitochondria and
affect metabolism at the most basic level. Research with
MOTS-c has been shown to promote the
burning of fat and sugar in mitochondria
by activating the AMPK pathway[6],
[7]. This is similar to what happens in
ketogenic diets like the Atkin’s diet, but
without the need to radically alter what
LEARN
MORE >>
you eat.
5-Amino-1MQ (NNMT Inhibitor)
5-Amino-1MQ (5-amino-1-methylquinolinium) inhibits
an enzyme known as NNMT. NNMT regulates the futile
cycle, which our bodies use when we are cold to convert
energy to heat. The futile cycle is highly effective at
burning fat, but NNMT turns this cycle off. Reasearch
shows that 5-Amino-1MQ blocks NNMT
and increases the rate of the futile
cycle. It also shows that 5-Amino-1MQ
causes dramatic weight loss in mouse
LEARN
<< MORE
models – as much as 35% fat loss in just
11 days[8]–[10]. As an added bonus,
5-Amino-1MQ lowers total cholesterol
levels significantly[10].
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
21
cha pt er t w o
Hormone Research and Hunger
We tend to think of hunger as our bodies telling us we need energy,
but that isn’t quite true. Hunger is controlled by a complex array
of hormones and neurotransmitters in our brains that evaluate
everything from the time of day to the mood we are in. The signals
our stomach sends to our brain to tell us we are hungry are also
susceptible to dysregulation by a number of factors including
age, insulin sensitivity, hormone levels, and more. The drive to
eat can be triggered not just by a low energy state, but by various
sights, sounds, smells, and even emotions. Controlling hunger is
no simple task, especially when it becomes dysregulated.
Research shows that a number of peptides and neurotransmitters
play a role in hunger and food cravings. They can prompt us to
eat less and can even affect the kinds of food we prefer, leading
us to choose more nutritious foods over fatty foods. Common
targets for suppressing hunger in animal studies include the GLP1 receptor, the GIP receptor, and the dopamine receptor in the
brain.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
22
cha pt er t w o
Semaglutide (GLP-1 Receptor Agonist)
Semaglutide is an agonist of the GLP1 receptor and works in two different
ways. First, Semaglutide can delay
gastric emptying and slow intestinal
motility
(movement)
to
increase
LEARN
MORE >>
feelings of fullness and decrease
the rate of rise of blood sugar.
Second, Semaglutide can act as a
neurotransmitter to reduce the drive
to eat in the brain. Research has shown it to produce a
5% weight loss over 6 months and average weight loss
of 15% at one year[11].
Tirzepatide (GLP-1 and GIP Receptor Agonist)
Tirzepatide is a peptide that interacts
with both the GLP-1 receptor and
the GIP receptor (i.e. twincretin).
It is similar to Liraglutide and
Semaglutide, but with additional
properties. Compared to strict GLP-1
LEARN
MORE >>
receptor agonists, Tirzepatide has
been show to be nearly 33 times more
likely to produce weight loss of 15% or
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
23
more. Tirzepatide acts on the GLP-
HAS S HOW N T O B E 3 3 %
1 receptor in the central nervous
TI MES MOR E L IKEL Y T O
P ROD UCE TO W EIGHT L O S S
OF 15% O R MO R E.”
cha pt er t w o
“TI RZEPA TID E R ES EAR C H
system to curb appetite and on
the GIP receptor in the gut to boost
insulin release and inhibit gastrin
release. Tirzepatide research has
shown to promote an average
weight loss of 11 kg (25 lbs) over 12 months[13], [14].
It also lowers triglycerides and other factors that are
associated with heart disease[12].
Tesofensine
Tesofensine
is
a
dopamine-
serotonin-norepinephrine (triple)
reuptake inhibitor. Originally being
studied for Parkinson’s Disease,
LEARN
MORE >>
Tesofensine was quickly identified
as a potential weight loss product
when its most common “side
effect” turned out to be weight
loss. Research in mice shows that Tesofensine regulates
appetite and food cravings to decrease energy intake.
Tesofensine research has been shown to promote a
10.6% weight loss over 24 weeks[15], [16]. It is thought
that Tesofensine suppresses appetite by increasing
dopamine levels in the brain[17].
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
24
03
CONCLUSION
03
CONCLUSION
Gaining weight as we age is an all-too-common problem
that is associated with changes in exercise capacity,
decreased energy levels, impaired heart health, and
waning cognitive function. We once blamed all of these
changes on the ravages of aging, but have discovered
that they may have more to do with declining hormone
levels. In fact, animal research has started to reveal
that these “inevitable” consequences of aging may
actually be preventable or even reversible.
Peptide research is untangling the mystery of how
we regulate weight. It is leading to discoveries that
may make it possible for us live longer, healthier
lives. Animal studies have demonstrated that we can
regulate energy balance, improve cardiac health,
boost fat burning, and build more muscle through the
scientific application of peptides. Ongoing research
with peptides is helping us to understand what causes
our bodies deteriorate as we age. This research may
eventually usher in a new era of wellness by not only
increasing life span, but by increasing health span as
well. Peptide research is unlocking the science to living
long, healthy, fulfilling lives.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
26
04
RESOURCES
04
RESOURCES
[1]
“Middle-Age
Weight
Gain
Study.”
https://www2.lbl.gov/Science-Articles/Archive/spare-tire.html
(accessed Apr. 21, 2022).
[2]
M. Heffernan et al., “The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism
following chronic treatment in obese mice and beta(3)-AR knock-out mice,” Endocrinology, vol. 142, no. 12, Art.
no. 12, Dec. 2001, doi: 10.1210/endo.142.12.8522.
[3]
N. B. Andersen, K. Malmlöf, P. B. Johansen, T. T. Andreassen, G. Ørtoft, and H. Oxlund, “The growth
hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult
rats,” Growth Horm. IGF Res., vol. 11, no. 5, Art. no. 5, Oct. 2001, doi: 10.1054/ghir.2001.0239.
[4]
J. V. Gobburu, H. Agersø, W. J. Jusko, and L. Ynddal, “Pharmacokinetic-pharmacodynamic modeling of
ipamorelin, a growth hormone releasing peptide, in human volunteers,” Pharm. Res., vol. 16, no. 9, Art. no. 9,
Sep. 1999, doi: 10.1023/a:1018955126402.
[5]
J. Svensson et al., “The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral
content in adult female rats,” J. Endocrinol., vol. 165, pp. 569–77, Jul. 2000.
[6]
K. H. Kim, J. M. Son, B. A. Benayoun, and C. Lee, “The Mitochondrial-Encoded Peptide MOTS-c Translocates
to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress,” Cell Metab., vol. 28, no.
3, pp. 516-524.e7, Sep. 2018, doi: 10.1016/j.cmet.2018.06.008.
[7]
C. Lee, K. H. Kim, and P. Cohen, “MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat
metabolism,” Free Radic. Biol. Med., vol. 100, pp. 182–187, Nov. 2016, doi: 10.1016/j.freeradbiomed.2016.05.015.
[8]
D. Kraus et al., “Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity,”
Nature, vol. 508, no. 7495, Art. no. 7495, Apr. 2014, doi: 10.1038/nature13198.
[9]
N. Klimova, A. Long, and T. Kristian, “Nicotinamide mononucleotide alters mitochondrial dynamics
by SIRT3-dependent mechanism in male mice,” J. Neurosci. Res., vol. 97, no. 8, Art. no. 8, 2019, doi: 10.1002/
jnr.24397.
[10]
H. Neelakantan et al., “Selective and membrane-permeable small molecule inhibitors of nicotinamide
N-methyltransferase reverse high fat diet-induced obesity in mice,” Biochem. Pharmacol., vol. 147, pp. 141–
152, Jan. 2018, doi: 10.1016/j.bcp.2017.11.007.
[11]
D. H. Ryan, “Drugs for Treating Obesity,” Handb. Exp. Pharmacol., Nov. 2021, doi: 10.1007/164_2021_560.
[12]
S. Urva et al., “The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
(GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1
receptor agonists,” Diabetes Obes. Metab., vol. 22, no. 10, pp. 1886–1891, Oct. 2020, doi: 10.1111/dom.14110.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
28
04
RESOURCES
[13]
B. Ludvik et al., “Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin
with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label,
parallel-group, phase 3 trial,” Lancet Lond. Engl., vol. 398, no. 10300, pp. 583–598, Aug. 2021, doi: 10.1016/
S0140-6736(21)01443-4.
[14]
M. K. Thomas et al., “Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and
Insulin Sensitivity in Type 2 Diabetes,” J. Clin. Endocrinol. Metab., vol. 106, no. 2, pp. 388–396, Nov. 2020, doi:
10.1210/clinem/dgaa863.
[15]
A. Astrup, S. Madsbad, L. Breum, T. J. Jensen, J. P. Kroustrup, and T. M. Larsen, “Effect of tesofensine
on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind,
placebo-controlled trial,” Lancet Lond. Engl., vol. 372, no. 9653, Art. no. 9653, 29 2008, doi: 10.1016/S01406736(08)61525-1.
[16]
A. Astrup, D. H. Meier, B. O. Mikkelsen, J. S. Villumsen, and T. M. Larsen, “Weight loss produced by
tesofensine in patients with Parkinson’s or Alzheimer’s disease,” Obes. Silver Spring Md, vol. 16, no. 6, Art. no.
6, Jun. 2008, doi: 10.1038/oby.2008.56.
[17]
A. M. D. Axel, J. D. Mikkelsen, and H. H. Hansen, “Tesofensine, a novel triple monoamine reuptake inhibitor,
induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor
pathways in the diet-induced obese rat,” Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol.,
vol. 35, no. 7, Art. no. 7, Jun. 2010, doi: 10.1038/npp.2010.16.
[18]
K. Raun et al., “Ipamorelin, the first selective growth hormone secretagogue,” Eur. J. Endocrinol., vol.
139, no. 5, Art. no. 5, Nov. 1998, doi: 10.1530/eje.0.1390552.
[19]
N. K. Aagaard et al., “Growth hormone and growth hormone secretagogue effects on nitrogen balance
and urea synthesis in steroid treated rats,” Growth Horm. IGF Res., vol. 19, no. 5, Art. no. 5, Oct. 2009, doi:
10.1016/j.ghir.2009.01.001.
[20]
E. Adeghate and A. S. Ponery, “Mechanism of ipamorelin-evoked insulin release from the pancreas of
normal and diabetic rats,” Neuro Endocrinol. Lett., vol. 25, no. 6, pp. 403–406, Dec. 2004.
[21]
D. E. Beck, W. B. Sweeney, M. D. McCarter, and Ipamorelin 201 Study Group, “Prospective, randomized,
controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative
ileus in bowel resection patients,” Int. J. Colorectal Dis., vol. 29, no. 12, Art. no. 12, Dec. 2014, doi: 10.1007/
s00384-014-2030-8.
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
29
04
RESOURCES
[22]
M. Alba et al., “Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone
(GHRH) analog, normalizes growth in the GHRH knockout mouse,” Am. J. Physiol. Endocrinol. Metab., vol. 291,
no. 6, pp. E1290-1294, Dec. 2006, doi: 10.1152/ajpendo.00201.2006.
[23]
V. A, C. G, B. A, G. G, A. Pg, and G. Ar, “Clinical use of growth hormone-releasing factor for induction
of superovulation.,” Hum. Reprod. Oxf. Engl., vol. 6, no. 9, Art. no. 9, Oct. 1991, doi: 10.1093/oxfordjournals.
humrep.a137517.
[24]
M. Ionescu and L. A. Frohman, “Pulsatile secretion of growth hormone (GH) persists during continuous
stimulation by CJC-1295, a long-acting GH-releasing hormone analog,” J. Clin. Endocrinol. Metab., vol. 91, no.
12, Art. no. 12, Dec. 2006, doi: 10.1210/jc.2006-1702.
[25]
A. Kannt et al., “A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of
metabolic disorders,” Sci. Rep., vol. 8, no. 1, Art. no. 1, 26 2018, doi: 10.1038/s41598-018-22081-7.
[26]
S. Imai and L. Guarente, “NAD+ and Sirtuins in Aging and Disease,” Trends Cell Biol., vol. 24, no. 8, Art.
no. 8, Aug. 2014, doi: 10.1016/j.tcb.2014.04.002.
[27]
K. F. Mills et al., “Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated
Physiological Decline in Mice,” Cell Metab., vol. 24, no. 6, Art. no. 6, 13 2016, doi: 10.1016/j.cmet.2016.09.013.
[28]
N. Klimova and T. Kristian, “Multi-targeted Effect of Nicotinamide Mononucleotide on Brain Bioenergetic
Metabolism,” Neurochem. Res., vol. 44, no. 10, Art. no. 10, Oct. 2019, doi: 10.1007/s11064-019-02729-0.
[29]
S. Tarantini et al., “Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular
endothelial function and neurovascular coupling responses and improves cognitive function in aged mice,”
Redox Biol., vol. 24, Apr. 2019, doi: 10.1016/j.redox.2019.101192.
[30]
I. a scraper, “Has Harvard’s David Sinclair Found the Fountain of Youth?,” Boston Magazine, Oct. 29,
2019. https://www.bostonmagazine.com/health/2019/10/29/david-sinclair/ (accessed Aug. 05, 2020).
Copyr igh t © 2023 | P EP T I D E SC I EN C ES. A ll r ig h t s r e s e r v e d .
30
PEPTIDESCIENCES.COM
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE
ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
THE PRODUCTS WE OFFER ARE NOT INTENDED FOR HUMAN USE DIRECTLY. THEY ARE INTENDED FOR IN-VITRO AND PRE-CLINICAL
RESEARCH PURPOSES ONLY. THESE PRODUCTS ARE NOT MEDICINES OR DRUGS AND HAVE NOT BEEN APPROVED BY THE FDA TO PREVENT,
TREAT OR CURE ANY MEDICAL CONDITION, AILMENT OR DISEASE.