Santa Fe Institute Collaboration Platform

COMPLEX TIME: Adaptation, Aging, & Arrow of Time

Get Involved!
Contact: Caitlin Lorraine McShea, Program Manager, cmcshea@santafe.edu

A theory of age-dependent mutation and senescence

From Complex Time
Revision as of 02:33, April 10, 2019 by OphelieRonce (talk | contribs) (Created page with "{{Reference Material |Meeting=Hallmarks of Biological Failure |Added by=OphelieRonce |title=A theory of age-dependent mutation and senescence |type=journal |year=2008 |source...")

(diff) ← Older revision | Approved revision (diff) | Latest revision (diff) | Newer revision → (diff)
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.

Counts

Citation count From Scopus. Refreshed every 5 days.
Page views
0

Identifiers

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

Add a file