evolutionary theories of ageing 02/04

Question 1

Define ageing

Answer 1

The progressive loss of function accompanied by declining fertility and increasing mortality with advancing age

Question 2

What is the ‘mutation accumulation’ theory of ageing?

Answer 2

This theory states that deleterious alleles that exert their effects later in life accumulate over generations. Many animals in the wild do not long surpass reproductive age due to extrinsic mortality (environmental hazards). This results in a ‘selection shadow’, where mutations beneficial only in later life are not selected for - neither are genes deleterious only in later life.

Question 3

What is the ‘antagonistic pleitrophy’ theory of ageing?

Answer 3

It provides genetic explanation for ‘fitness trade-offs’. It refers to the phenomena of a gene controlling more than one phenotypic trait, where one trait is beneficial and one is deleterious. If benefits occur early in life and deleterious effects late in life, then the gene will be selected for. The theory particularly refers to traits which increase fertility or reproductive potential early in life.

Because the contribution to fitness is a composite of both the size of the effect and the probability of surviving to be affected by it, a small beneficial effect early in life can outweigh a late deleterious effect even if the latter results in senescence and death.

Question 4

Define the ‘disposable soma’ theory of ageing

Answer 4

The disposable soma theory of aging acts on the premise that there is a tradeoff in resource allocation between somatic maintenance and reproductive investment. Too low an investment in self-repair would be evolutionarily unsound, as the organism would likely die before reproductive age. However, too high an investment in self-repair would also be evolutionarily unsound due to the fact that one’s offspring would likely die before reproductive age. This results in accumulation of deleterious cell effects.

It is a similar theory to antagonistic pleitrophy, however it refers specifically to cellular mechanisms.

Question 5

What are three predictions of evolutionary theories of ageing?

Answer 5

1. Specific genes selected to promote ageing are unlikely to exist e.g., Ageing does not serve the function of limiting population or increasing genetic turnover
2. Ageing is not programmed but results largely from accumulation of somatic damage, owing to limited investments in maintenance and repair. Longevity is thus regulated by genes controlling levels of activities such as DNA repair and antioxidant defence. - Species with higher extrinsic mortality will therefore show reduced soma maintenance mechanisms.
3. There may be adverse gene actions at older ages arising either from purely deleterious genes that escape the force of natural selection or from pleiotropic genes that trade benefit at an early age against harm at older ages. If it stems from pleitrophy, then this would predict that increased species lifespan results in decreased species fertility.

Question 6

What are three pieces of experimental evidence that support evolutionary theories of ageing?

Answer 6

Artificial delaying of selection pressures in drosophilia. By restricting mating to later life, selection pressure is increased in later life. Drosophilia experiments show that restricting mating to later life causes not only increased longevity in offspring populations but also shows evidence of ‘trade-offs’ such as reduced early fecundity and reduced larval viability. Depression of early fitness traits allows for increased longevity - because antagonistic pleitropic genes are now selected against.

Cell and DNA maintainence levels correlate with maximum longevity. Rodent species with higher longevity show lower generation of the reactive oxygen species (ROS) e.g., H202, higher cellular concentrations of some antioxidant enzymes such as SOD, and overall lower levels of protein oxidative damage. DNA repair capacity also correlates with longevity across species, as do levels of enzymes necessary for maintainence of genomic integrity. Cell cultures from longer lived species are shown to be more robust against envionrmental stressors, supporting that these adaptions serve to promote longevity.

Across species, longevity correlates wiht fertility. Mice are short lived and highly fertile. In man, they are long lived and relatively infertile. Women who live to older ages also show reduced levels of fertility.

Question 7

Examples of antagonistic pleitrophic genes

Answer 7

oestrogen:
early life =reproduction
late life = cancer

sickle trait:
early = protect from malaria
late = haemorrhage, organ failure

Huntingtin gene:
early life= greater fertility
late = cognitive & movement disorders