Hematopoietic Stem Cell Quiescence Attenuates DNA Damage Response and Permits DNA Damage Accumulation During Aging

• DOI: 10.4161/cc.6.19.4759
• Publication Date: 2010-08-18T15:06:19Z
• Authors: Derrick J. Rossi; Jun Seita; Agnieszka Czechowicz; Deepta Bhattacharya; David Bryder; Irving L. Weissman
• Keywords: Hematopoietic stem cell; Senescence

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