Making ends meet in old age: DSB repair and aging

Mech Ageing Dev. 2005 Jun-Jul;126(6-7):621-8. doi: 10.1016/j.mad.2005.02.008. Epub 2005 Mar 24.

Abstract

Accumulation of somatic mutations has long been considered as a major cause of aging and age-related diseases such as cancer. Genomic rearrangements, which arise from aberrant repair of DNA breaks, are the most characteristic component of the mutation spectra in aging cells and tissues. The studies conducted in the past few years provide further support for the role of DNA double-strand break (DSB) repair in aging and cellular senescence. Evidence was obtained that in addition to accumulation of mutations the efficiency and fidelity of repair declines with age. We propose that DNA damage and age-related decline of DNA repair form a vicious cycle leading to amplification of damage and progression of aging, and discuss a hypothesis on how the interplay between the two pathways of DSB repair, homologous recombination and nonhomologous end joining, may contribute to the aging process.

Publication types

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

MeSH terms

  • Animals
  • Cellular Senescence / genetics
  • Cellular Senescence / physiology*
  • DNA Damage / genetics
  • DNA Damage / physiology*
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • Humans
  • Recombination, Genetic / genetics
  • Recombination, Genetic / physiology*