A test of evolutionary theories of aging

Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14286-91. doi: 10.1073/pnas.222326199. Epub 2002 Oct 17.


Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. The two leading theories posit that aging is due to (i) pleiotropic genes with beneficial early-life effects but deleterious late-life effects ("antagonistic pleiotropy") or (ii) mutations with purely deleterious late-life effects ("mutation accumulation"). Previous attempts to distinguish these theories have been inconclusive because of a lack of unambiguous, contrasting predictions. We conducted experiments with Drosophila based on recent population-genetic models that yield contrasting predictions. Genetic variation and inbreeding effects increased dramatically with age, as predicted by the mutation theory. This increase occurs because genes with deleterious effects with a late age of onset are unopposed by natural selection. Our findings provide the strongest support yet for the mutation theory.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / genetics*
  • Aging / physiology
  • Animals
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology
  • Evolution, Molecular*
  • Female
  • Inbreeding
  • Male
  • Reproduction / physiology