A theory of age-dependent mutation and senescence
- General Reference
- author-supplied keywords
- A theory of age-dependent mutation and senescence
Laboratory experiments show us that the deleterious character of accumulated novel age-specific mutations is reduced and made less variable with increased age. While theories of aging predict that the frequency of deleterious mutations at mutation-selection equilibrium will increase with the mutation's age of effect, they do not account for these age-related changes in the distribution of de novo mutational effects. Furthermore, no model predicts why this dependence of mutational effects upon age exists. Because the nature of mutational distributions plays a critical role in shaping patterns of senescence, we need to develop aging theory that explains and incorporates these effects. Here we propose a model that explains the age dependency of mutational effects by extending Fisher's geometrical model of adaptation to include a temporal dimension. Using a combination of simple analytical arguments and simulations, we show that our model predicts age-specific mutational distributions that are consistent with observations from mutation-accumulation experiments. Simulations show us that these age-specific mutational effects may generate patterns of senescence at mutation-selection equilibrium that are consistent with observed demographic patterns that are otherwise difficult to explain.
- Citation count From Scopus. Refreshed every 5 days.
- Page views
- 4Error!"Error!" can not be assigned to a declared number type with value 4.
- doi: 10.1534/genetics.108.088526 (Google search)
- issn: 00166731
- sgr: 55749090979
- scopus: 2-s2.0-55749090979
- pui: 354162653