DNA double-strand breaks: A potential causative factor for mammalian aging?

Han Li, James R. Mitchell, Paul Hasty

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Aging is a pleiotropic and stochastic process influenced by both genetics and environment. As a result the fundamental underlying causes of aging are controversial and likely diverse. Genome maintenance and in particular the repair of DNA damage is critical to ensure longevity needed for reproduction and as a consequence imperfections or defects in maintaining the genome may contribute to aging. There are many forms of DNA damage with double-strand breaks (DSBs) being the most toxic. Here we discuss DNA DSBs as a potential causative factor for aging including factors that generate DNA DSBs, pathways that repair DNA DSBs, consequences of faulty or failed DSB repair and how these consequences may lead to age-dependent decline in fitness. At the end we compare mouse models of premature aging that are defective for repairing either DSBs or UV light-induced lesions. Based on these comparisons we believe the basic mechanisms responsible for their aging phenotypes are fundamentally different demonstrating the complex and pleiotropic nature of this process.

Original languageEnglish (US)
Pages (from-to)416-424
Number of pages9
JournalMechanisms of Ageing and Development
Volume129
Issue number7-8
DOIs
StatePublished - Jul 2008

Keywords

  • Apoptosis
  • Cellullar senescence
  • DNA damage response
  • Double-strand breaks
  • Nonhomologous end joining

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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