Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging
(2007) In Cell Cycle 6(19). p.2371-2376- 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 (G(0)) cell cycle status of HSC, which results in an attenuation of checkpoint control and DNA damage responses for repair or apoptosis. When aged... (More)
- 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 (G(0)) 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/969196
- author
- Rossi, Derrick J. ; Seita, Jun ; Czechowicz, Agnieszka ; Bhattacharya, Deepta ; Bryder, David LU and Weissman, Irving L.
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- hematopoietic, genomic instability, quiescent, aging, genomic, maintenance
- in
- Cell Cycle
- volume
- 6
- issue
- 19
- pages
- 2371 - 2376
- publisher
- Landes Bioscience
- external identifiers
-
- wos:000251085700012
- scopus:35848943667
- ISSN
- 1551-4005
- language
- English
- LU publication?
- yes
- id
- f9ed31c8-5acd-4949-82c1-28989a519ef8 (old id 969196)
- alternative location
- http://www.landesbioscience.com/journals/cc/article/4759
- date added to LUP
- 2016-04-01 11:41:13
- date last changed
- 2022-01-26 08:44:53
@article{f9ed31c8-5acd-4949-82c1-28989a519ef8,
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 (G(0)) 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.}},
author = {{Rossi, Derrick J. and Seita, Jun and Czechowicz, Agnieszka and Bhattacharya, Deepta and Bryder, David and Weissman, Irving L.}},
issn = {{1551-4005}},
keywords = {{hematopoietic; genomic instability; quiescent; aging; genomic; maintenance}},
language = {{eng}},
number = {{19}},
pages = {{2371--2376}},
publisher = {{Landes Bioscience}},
series = {{Cell Cycle}},
title = {{Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging}},
url = {{http://www.landesbioscience.com/journals/cc/article/4759}},
volume = {{6}},
year = {{2007}},
}