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• W1546773198 abstract "Several lines of evidence suggest that the accumulation of DNA damage contributes to organismal aging. Telomere dysfunction, replication errors and toxic metabolites (possibly including reactive oxygen species) represent some of the causes contributing to DNA damage accumulation during aging. DNA damage induces checkpoint responses such as cell cycle arrest or apoptosis. These checkpoints protect the aging organism against cancer but at the same time could contribute to the decline of tissue maintenance and organ function during aging, likely involving an impaired maintenance of functional stem cells. In addition, there is experimental evidence that a tight regulation of cell cycle activity is required to maintain adult stem cells during aging. At the Else KrOner-Fresenius Symposium on the Molecular Mechanisms of Stem Cell Aging, several speakers addressed the role of DNA damage and checkpoint responses in stem cell aging. In this chapter, we review some of the new aspects from the meeting, showing that: (1) stem cells are more resistant to DNA damageinduced checkpoints and exhibit an increased accumulation of DNA damage compared to progenitor cells; (2) deletion of PUMA allows hematopoietic stem cells to survive in response to irradiation-induced DNA damage; (3) p53-dependent checkpoints can protect tissues from age-related atrophy by depleting chromosomally unstable stem cells; (4) Chk2-dependent checkpoints limit progenitor cell function in response to DNA damage induced by reactive oxygen species; (5) genetic modifiers influence the functional role of checkpoint genes in stem cells; (6) FoxO-dependent restriction of cell cycle activity maintains neuronal stem cells, and (7) DNA repair by homologue recombination is required for hematopoietic stem cell expansion and maintenance." @default.
• W1546773198 created "2016-06-24" @default.
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• W1546773198 date "2010-01-01" @default.
• W1546773198 modified "2023-09-25" @default.
• W1546773198 title "DNA Damage, Checkpoint Responses, and Cell Cycle Control in Aging Stem Cells" @default.
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• W1546773198 doi "https://doi.org/10.1159/000312653" @default.
• W1546773198 hasPublicationYear "2010" @default.
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