Aging Lecture

extrinsic mortality

death through environmental causes, such as accidents, predation, or infection

what does high extrinsic mortality mean?

means that few individuals survive to old age in natural populations because selective populations were not operating on genes as you got older since predators were taking care of that

mutation accumulation

old age is a ‘blind spot’ for selection. the force of selection weakens with age

Why is the force of selection on late-life acting mutations weak?

because few individuals live long enough for those mutations to have negative effects. before the negative effects, individuals are likely to have already reproduced and passed down those mutations

what does the selective shadow in the graph represent?

• shows selective shadow in old age allows for alleles with deleterious effects on fitness in later life to accumulate within the genome 

• If I have children before I’m old, I pass on any genes I have, whether they are good or bad for being old because selection operates on reproductive success → evolution only cares about life span to ensure that span includes reproduction

mutation accumulation theory

selection in old age is too weak to purge mutations affecting only late life

antagonistic pleiotropy

weakening of selection means that “mutations with fitness benefits in early life but costs in late life” are favored

disposal soma hypothesis

selection favors the sacrifice of long-term maintenance and repair in exchange for early-life reproductive fitness

What factors extend lifespan and alleviate age-related declines in function in the lab?

• Diet, drug, and genetic manipulation of nutrient sensing pathways

• single gene mutations and dietary restriction extend lifespan

rapamycin

• drug that messes with mTOR, which is important in cell proliferation

• it suppresses cellular proliferation and super oxidative stress

  • oxidative damage is handled at maintenance level of cell, which contributes to longer

• can stunt growth

• anti-aging intervention that is directed towards nutrient sensing pathways

what did rapamycin do in model organisms (with mice)?

extended survival time in the mice

How does dietary restriction (DR) inhibit TOR?

• DR leads to glycogen accumulation, glycerol accumulation, etc.

• cells police within the cell more effectively

what are challenges of the model organism approach?

• Model organisms are very short lived species → selection on life history and aging will vary depending on lifespan 

• Often inbred or lab-adapted → genetic variation may not be representative of anything in natural conditions 

• Lab environment totally unlike nature → life histories and aging rates are extremelly plastic; strategy favoured by selection may depend on environmental conditions

• Lab organisms can’t tell us how they feel

what are benefits of model organism work?

provides strong support for antagonistic pleitropoy/disposable soma ideas

what increases the declining rate of the strength of natural selection with age?

• Increased extrinsic mortality 

• If you are likely to be murdered young, the speed at which you age will increase 

• There is less selection if you die younger

• Result = selection for more rapid senescence but only if mortality is applied randomly

what does high mortality lead to?

increased investment in reproduction