Searching for the
Fountain of Youth
Senescence: Why do
developmental processes fail to
maintain the accomplishments of
their own work?
Bacteria (blue(blue-green algae)
Comparative Gerontology:
N allll species
Not
i appear to age, some
organisms display
negligible senescence
Prokaryotic Microorganisms
Fungus
• Cell division by fission: A mother cell
divides into two equal daughter cells.
• It is not possible to distinguish progenitor
f
from
offspring.
ff i
• These cells have the ability to divide
eternally without loss of viability.
• Protected from violent death, bacteria are
• Fungus show signs of aging.
• The oldest known fungus (Armillaria
ostoyae) is between 2,400 to 7,200 years
old.
immortal.
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One member of this species is the
largest organism on earth.
Plants
• Aging in plants may be difficult to define.
• Some trees are generated on the roots of
The honey mushroom fungus growing 3 feet underground
in Oregon’s Malheur National Forest covers 2,200 acres.
Bristlecone Pine:
Longevity 4,731 years
(no signs of senescence)
Invertebrate Animals with
Negligible Senescence
another tree. Are the two trees one plant or
t ? Wh
two?
When the
th first
fi t tree
t
di
dies, is
i the
th second
d tree
t
now another tree or still the same tree?
• Grafting may have no time limit in some species,
while the viability of cuttings may decrease with
age in other species (sugar cane).
Bamboo are semelparous
(reproduce once and die): the age
to reproduction varies by species 7
– 120 years.
Antarctic Sponges:
Longevity 23,000 years
(This is a record for animals)
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Red Sea Urchin:
Longevity 200 Years
Vertebrate Animals with
Negligible Senscence
Rougheye rockfish: longevity 205 years
Painted Turtle: longevity 61 years
(similar to red snapper in size and appearance)
(many reptiles and amphibians show low
rates of senescence)
Eastern Box Turtle: Longevity 138 years
Some Organisms seem to age
extremely rapidly
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Turquoise Killifish:
The vertebrate with the shortest
known lifespan
(Longevity 12 weeks)
Mechanical Senescence: some
protozoans reproduce by budding,
but are born without any means to
dispose of wastes. Thus individual
cell death is inevitable.
Life history strategies appear to
impact
p
on the presence,
p
absence or
rate of senescence.
Clonal or reduplicative senescence:
cells born from older individuals
have shorter lifespans. After
hundreds of generations of asexual
reproduction
d i clonal
l
l extinction
i i may
be reached (e.g. paramecium).
After sex in paramecium (genetic
material is exchanged) the cells are
reproductively rejuvenated.
Paramecium
Insects: In some species the molt
to adult forms (Mayfly) is
characterized by aphagy, a form of
mechanical
h i l senescence,
senescence, where
h
the mouthmouth-parts or gut are
defective and the adult is incapable
of ingesting a meal.
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Mayfly
Insects: The exoskeleton is mostly
composed of post
post--mitotic tissue. It
is susceptible to wear but
cannot be repaired or replaced.
replaced.
In ants the queens may live for
over 15 years. They are groomed
by workers and their bodies do not
wear out as quickly.
Fish: Rockfish show no signs of
reproductive senescence and grow
continuously.
In Pacific salmon rapid senescence
follows reproduction: a hormonal
cascade triggers reproduction, the
adults stop eating
eating, develop many
pathologies, and soon die. (Does
their rotting flesh feed insects that
are critical for the survivorship of
the fry?)
King salmon
Fish: In some founder
founder--like fish the
females continue to grow and show
no signs of aging,
aging while the males
stop growing, age and die. Does
the cessation of grown lead to
scenescence?
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Walleye Pike
Walleye: Depending on lake
temperature its lifespan can
increase fivefold.
fivefold. Decreased
rates of maturity and increased
lifespan are a result of lower
temperature.
Reptiles and Amphibians: Show a
less intense aging phenotype with
many species failing to show a
characteristic maximum lifespan.
Pigeons
( a representative galliform)
Birds: Some species show
accelerated mortality with age
(galliforms),
(g
), while other species
p
show very long lifespans with little
signs of reproductive senescence.
Andean Condor: Longest lived bird
(75 years). Birds do not have
continuous growth. There are no
reports of birds with negligible
senescence.
senescence
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Mammals: A few mammals show
semelparity: The Australian mouse
have such a heightened libido that
the males are unable to eat, and
eventually
ll di
die off sexuall stress.
Australian Mouse
• All the males die after breeding from
parasites in the blood and intestines.
(The immune system fails when the
exhaustion stage is reached in the General
Adaptation Syndrome). Many females die
after rearing their first litter.
Bowhead Whale: The longest lived
mammal with a lifespan exceeding
200 years.
Primates: Chimpanzees show age
age-related changes typical to humans,
but at much younger ages. The
chimp longevity record is 73 years.
Humans are the primate with the
l
longest
lifespan.
lif
Jeanne
J
Calment
C l
died at 122 years of age in 1998,
and is the believed to be the
current primate record holder for
longevity.
Tooth Erosion:
Erosion: A form of
mechanical senescence that may
set an upper limit for longevity in
some mammals (elephants, horses,
hippos, ancestral humans).
humans).
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All mammals show reproductive
senescence,, an increase in
senescence
mortality with age, and evidence of
functional decline with age.
g The
patterns of female reproductive
senescence at midmid-life,
osteoporosis, arthritis, vascular
lesions and cataracts are quite
common among mammals.
Theory of Programmed Death
Weismann: “The unlimited
existence of individuals would be a
luxury without any corresponding
advantage. Death is an adaptation
advantageous to the race” (or
species). This assumes that
selection is operating at the group
level.
Brown’s Theory of Kin Inflicted Death:
How is the fitness of the progeny
influenced if the adults live too long
post--reproductively? Conflict in
post
interests between generations. As the
progeny mature, their fitness becomes
l
less
dependent
d
d t upon parental
t l care, and
d
more dependent upon the availability
of reproductive vacancies. Traits which
would favor a timely transition
(between generations) may be
selected.
Theories of Senescence
1. Theory of Programmed Death
2. Mutation Accumulation Theory
3. Antagonistic Pleiotropy Theory
Weismann: “When one or more
individuals have provided a
sufficient number of successors
they themselves, as consumers of
nourishment in a constant changing
d
degree,
are an injury
i j
to those
h
successors.” This assumes that
death is favored by kin selection.
(Does fecundity decrease if the old
live too long?)
Mutation Accumulation Theory:
Aging is a result of the decrement
in the significance of a deleterious
gene with increasing
g
g age.
g Over
successive generations late acting
mutations will accumulate, leading
to increased mortality rates late in
life.
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Antagonistic Pleiotropy Theory:
Late acting deleterious mutations
may even be favored by selection
if theyy yyield benefits earlyy in life.
Also known as the (i) disposable
soma theory, (ii) Orgel’s error
catastrophe theory, and the (iii)
pay--later theory.
pay
Tests of the Theories of Aging
Programmed Death:
Is there a limit on cell divisions?
(Do you run out of life and die?)
E l Swim:
Earle
S i
tissue
i
culture
l
experiments:
Phase I: rapid cell proliferation.
Phase II: decrease in proliferation
until a point where it ceases and
cells are lost as a result of
nonspecific degeneration. Phase
III: (rare) remaining cells differ in
both morphology and growth
pattern from the initial culture.
The limit in duplication is also
known as the Hayflick limit.
Because cell division stops, but no
programmed death occurred this
finding was thought to disprove the
programmed
d death
d h hypothesis.
h
h i
However, under natural conditions
the loss of the capacity for tissue
repair would hasten death.
Programmed Death:
The ageage-dependence of death rates
should increase dramatically when
the alleged death program comes
into action. A mortality explosion is
seen in semelparious species but is
not strongly displayed in
iteroparious species. It is not clear
how dramatic the death explosion
needs to be to support the
programmed death theory.
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Mutation Accumulation Theory:
Predicts that the frequency of
genetic diseases should increase
g
with older ages. Death rate data
for European royal families are in
agreement with this prediction.
Antagonistic Pleiotropy Theory:
Pleiotropy means that a single gene
may have an effect on multiple
traits of an organism. Pleiotropic
effects may affect individual fitness
in antagonistic ways. Natural
selection may favor vigor in youth
over old age when ever a conflict in
interests arise.
(e.g. mutations favoring over production of
sex hormones may amplify reproductive
fitness in youth, but result in prostate
cancer in males, and ovarian cancer in
females later in life).
Predictions: (1) rapid individual
development should be correlated with rapid
senescence, and (2) selection for increased
l
longevity
it should
h ld result
lt in
i decreased
d
d vigor
i
in
i
youth (confirmed in fruit flies).
Antagonistic Pleiotropy Theory:
Prediction: senescence should be a
generalized deterioration, and
never due to changes in a single
system banishing the concept of
the fountain of youth.
Conclusions
Aging is a product of evolutionary
forces, not biochemical or cellular
quirks. The life historyy strategies
q
g
of some organisms are associated
with rapid senescence, while other
organisms appear to show little
signs of aging.
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Conclusions
Conclusions
There may be no single universal
theory of aging. Different theories of
aging may apply to different species
with different life history strategies.
Recent discoveries of lifelife-extending
mutations are inconsistent with
both the mutation accumulation
and antagonistic pleiotropy
theories. Both theories predict that
no single treatment should
dramatically influence longevity.
Conclusions
Conclusions
Also inconsistent with these theories is
the observation that (within mammals)
the pattern of aging is similar across
species.
Because aging in mammals seems to
be confined to certain specific systems,
senescence may
• Be governed by a few genes
• Differ between species with different lifelifehistory strategies
• Be the product of group selection in some
species
Conclusions
• Questing for the fountain of youth may
yield
y e d ssignificant
g ca t lifelife
e- e
extending
te d g d
discoveries.
sco e es
• Advancements may lead to ethical
dilemmas.
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