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A theory of age-dependent mutation and senescence

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Category
General Reference
author-supplied keywords
keywords
authors
title
A theory of age-dependent mutation and senescence
type
journal
year
2008
source
Genetics
pages
2061-2073
volume
179
issue
4

Abstract

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.

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Identifiers

  • doi: 10.1534/genetics.108.088526 (Google search)
  • issn: 00166731
  • sgr: 55749090979
  • scopus: 2-s2.0-55749090979
  • pui: 354162653

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