the evolution of life span why do we live as long as we do?
TRANSCRIPT
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The Evolution of Life Span
Why do we live as long as we do?
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StressGenome Stress
DNA damageOxidative Stress
p53ApoptosisSenescenceGrowth Inhibition
The p53 Tumor Suppressor
- Loss of p53 function results in an increased incidence of cancer
- p53 is mutated in ~80% of all human tumors
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p53 may promote aging…
p53
Cancer Aging
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Why did we evolve a system thatlimits our lifespan?
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Evolution Basics
Natural Selection -The process by which the individual with the greatest fitness is selected from a population of genetically variable individuals of one species.
Fitness = reproductive success
Individuals with the best reproductive success have more offspring.And so on, and so on, until the adaptation (gene) that led to greater reproductive success is present throughout the species.
Evolution (natural selection) will only act on genes (traits) that lead to greater reproductive success.
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Evolutionary Theory of Life Span
- Huntington’s Disease, a dominant lethal mutationHow does Huntington’s stay in the population if it results in lethality?
Idea: Aging results from a decline in the force of natural selection.
%
10 20 30 40 50 60 70 80age in years
100
Natural Selection
Age of onset for Huntington’s = ~35yr
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%Alive
1 2 3 4 5 6 7 8age in years
100
Aging in Nature
- Most organisms do not age in a natural environment.
Life Span in the LabLife Span in Nature
Aging BeginsNatural Selection
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Lifespan is proportional to extrinsic mortality!
If mortality is high an organism will die frompredation or other hazards before it grows old.
-Therefore there is no reason to evolve a longlife span.
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Evolutionary Theories of Aging
Disposable Soma - Somatic cells are maintained only to ensure
continued reproductive success, following reproduction
the soma is disposable. (life span theory)
Antagonistic Pleiotropy - Genes that are beneficial at younger
ages are deleterious at older ages.
Mutation Accumulation - Mutations that affect health at older
ages are not selected against (no strong evidence).
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Evolutionary Theories of Aging
Nature 408, 233-38 (2000)
Mutation Accumulation
Disposable Soma WildProtected
Antagonistic Pleiotropy
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Traits That Correlate with Longevity
- Body weight, brain weight
- Length of growth period, prolonged adolescence*Brain Size*
- Can evolution theory help explain these correlations?
- Metabolic rate (inversely correlated)
- Fecundity, # of offspring (inversely correlated)
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Opossums and Life Span
- ultimate prey, ~ 80% die from predation- typically reproduce once- age very rapidly
-Hypothesis: The presence of predators limits life span, naturalselection favors somatic maintenance for only as long as an average opossum can be expected to live.
Steve Austad, U. of Idaho
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Sapelo Island Opossums
- no predators (out in daytime)- longer average life span- reproduce twice (fewer offspring/litter)
-Are these changes due to a lack of predators, or a physiological change that delays the aging process?
Physiological Change - Sapelo island opossums not onlylive longer, they age slower than mainland animals.
-Sapelo Island opossums have less molecular damage than mainland opossums.
(collagen X-linking)
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Evolution in the Laboratory%
Su
rviv
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Age in Days
~40d
Drosophila Survival Curve
Michael Rose, U.C. Irvine
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Evolution in the Laboratory
- Reproductive period extended- Stress resistant- Early adult fecundity reduced (antagonistic pleiotropy)
Offspring of “old” flies are selected
Normal
old flies selected
% S
urv
ivin
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Age in Days
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Evolution in the Laboratory
old flies selected
young flies selected
Normal
% S
urv
ivin
g
Age in Days
- Early adult fecundity increased (antagonistic pleiotropy)
Offspring of “young” flies are selected
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Summary of Drosophila Selection
1) Selection at age of reproduction can alter the lifespan of Drosophila (lifespan has been doubled by this technique).
2) Increase in lifespan has a cost, reduced fecundity (reproduction). - antagonistic pleiotropy -
3) Long-lived flies are stress resistant (heat shock, oxidants).
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Exceptions to the Rule
Some organisms evolve unique adaptations that allow the subsequent evolution of exceptional life span.
Rats and Bats: Rats live for ~3 years, Bats live for ~30 years
Bats evolved a mechanism (flight) that reduced extrinsic mortalityand allowed for the subsequent evolution of a long life span.
What other adaptations might lead to prolonged life span?
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Exceptional Life Span in Eusocial Insects
Queen Bees and Queen Ants have exceptional life spans!
•Small size •Many offspring
Why do they live so long?
- Protected from the environment, therefore extrinsic mortality is low!
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Keller L, Genoud M: Extraordinary lifespans in ants: A test of evolutionary theories of ageing. Nature (London) 1997, 389:958-960
20 301000
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Keller L, Genoud M: Extraordinary lifespans in ants: A test of evolutionary theories of ageing. Nature (London) 1997, 389:958-960
Exceptional Life Span is due to Social Organization
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What does this tell us about aging?
-Size is not necessarily important!
-Reproduction / metabolism does not control life span.•Some queen ants produce their body weight in offspring each day
-Life Span results from selective pressures.
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What about Humans?
-Unlike most animals, humans and some related primates age in a natural environment.
-Menopause is also unique to humans. How can nature select for a process that limits reproduction?
-How does parental care influence the evolution of human life span?
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Evolutionary models that integrate parental investment can moreaccurately predict age-specific mortality rates.
Age specific mortality in humans
Ronald Lee, UC Berkeley
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Life Span versus Aging
Aging - can not be selected for, results from an absenceof natural selection.
Life Span - results from a balance between two majorselective forces.
Environmental Selection - predators, natural hazards
Social Selection - parental investment, sexual behavior
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Main Ideas
1. Life span results from selective pressure.
2. Life span is inversely proportional to extrinsic mortality.
3. Aging results from a lack of natural selection with age.