Task 1
PS: What influences ageing?
Learning goals:
How does food influence ageing? (biological part as well)
What is the difference between animals and humans related to food
restriction and ageing?
What is the evolutionary explanation for ageing?
Why do we age?
What is the selection shadow?
Kirkwood *, T. B. L, & Austad, S. N. (2000). Why do we age? Nature, 408, 233-
238.
Ageing is defined as progressive loss of function, decreased fertility and
increased mortality. It is not universal, because some creatures don't show these
signs, so it is not an inevitable result of biological wear and tear.
Senescence = the process of deterioration with age.
Theories about the evolution of ageing:
- Programmed ageing: To limit population size, or accelerate the turnover of
generations. But there is not enough evidence that senescence contributes
significantly to mortality in the wild. Natural mortality is mostly due to extrinsic
hazards, e.g. infection, starvation. Therefore natural selection has limited
opportunity to exert a direct influence over the process of senescence. Wild
animals don't live long enough to grow old (fig. 1a).
- Mutation accumulation theory: As a result of extrinsic mortality, there's a
, progressive weakening in the force of selection with increasing age. By an age
when wild survivorship had declined to very low levels, the force of selection is
too weak to oppose the accumulation of germ-line mutations (mutatie die in
geslachtscellen terecht komt) with late-acting deleterious effects. The 'selection
shadow' allows a wide range of alleles with the late deleterious effects to
accumulate over generations with little or no check (fig 1b). Genes have
deleterious late effects. The harmful genes accumulate later in life, that is the
effect. Example: a defective gene in children will disappear. Genes can't be
reproduced after someone is not fertile anymore, so the genes can't be
reproduced.
(Er is een hoge mortaliteit door externe factoren, waardoor er steeds minder
invloed is van selectie door leeftijd. Als de kans op overleving in het wild erg klein
is , is de kracht van selectie te zwak om de opeenhoping van mutaties in de
geslachtscellen tegen te gaan die zorgen voor latere schadelijke effecten. In de
'selection shadow' kunnen veel late schadelijke effecten opeenhopen over
generaties, met weinig controle)
- Pleiotropy: pleiotropic genes (multiple effects from a single gene) with good
early effects would be favoured by selection, even if those genes would have
negative effects on later ages, even ageing or death (fig. 1c). Early investment
more important.
- Disposable soma theory: based on optimal allocation of metabolic resources,
between somatic maintenance and reproduction. Effective somatic maintenance
is required to keep the organism in a good physical condition, for as long as it can
survive in the wild (fig.1d). Mechanisms to combat intrinsic deterioration require
metabolic resources, which are scarce. In wild mice, 90% die after their first year,
so it's kind of a rule that it is not beneficial to repair the system. The main cause
of death is cold, because it requires thermogenesis. They invest all their spare
resources in to thermogenesis and reproduction, rather than into better repair
capacity, although the damage will later accumulate to cause ageing.
The difference with pleiotropy is that this theory focuses on the mechanisms
(metabolism), especially somatic maintenance and repair instead of the general
pattern of gene action (genetics).
Based on life-history trade-off, if the resources go to somatic maintenance or
reproduction. If you don't reproduce you'll have more resources for somatic
maintenance. When it's not worthwile to repair it anymore you age.
--> The principal determinant in the evolution of longevity is predicted to be the
level of extrinsic mortality. When this is high, life expectancy in the wild is
short, the force of selection attenuates fast, deleterious gene effects accumulate
at earlier ages, and there it little selection for a high level of somatic
maintenance. The organism is predicted to be short lived, even when studied in a
protected environment.
When extrinsic mortality is low, selection is predicted to postpone deleterious
gene effects and to direct greater investment in building and maintaining the
body.