Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging

Derrick J. Rossi, Jun Seita, Agnieszka Czechowicz, Deepta Bhattacharya, David Bryder, Iirving L. Weissman

Research output: Contribution to journalReview articlepeer-review

134 Scopus citations

Abstract

The aging of tissue-specific stem and progenitor cells is believed to be central to the pathophysiological conditions arising in aged individuals. While the mechanisms driving stem cell aging are poorly understood, mounting evidence points to age-dependent DNA damage accrual as an important contributing factor. While it has been postulated that DNA damage may deplete stem cell numbers with age, recent studies indicate that murine hematopoietic stem cell (HSC) reserves are in fact maintained despite the accrual of genomic damage with age. Evidence suggests this to be a result of the quiescent (G0) cell cycle status of HSC, which results in an attenuation of checkpoint control and DNA damage responses for repair or apoptosis. When aged stem cells that have acquired damage are called into cycle under conditions of stress or tissue regeneration however, their functional capacity was shown to be severely impaired. These data suggest that age-dependent DNA damage accumulation may underlie the diminished capacity of aged stem cells to mediate a return to homeostasis after acute stress or injury. Moreover, the cytoprotection afforded by stem cell quiescence in stress-free, steady-state conditions suggests a mechanism through which potentially dangerous lesions can accumulate in the stem cell pool with age.

Original languageEnglish (US)
Pages (from-to)2371-2376
Number of pages6
JournalCell Cycle
Volume6
Issue number19
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Keywords

  • Aging
  • Genomic instability
  • Genomic maintenance
  • Hematopoietic
  • Quiescent

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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