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首页> 外文期刊>Cell cycle >Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging.
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Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging.

机译：造血干细胞的静止减弱了DNA损伤的反应，并在衰老过程中积累了DNA损伤。

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摘要

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.
机译：组织特异性干细胞和祖细胞的衰老被认为是老年个体发生的病理生理状况的关键。尽管对干细胞衰老的机制知之甚少，但越来越多的证据表明，与年龄有关的DNA损伤是重要的促成因素。尽管已经假定DNA损伤会随着年龄的增长耗尽干细胞的数量，但最近的研究表明，尽管随着年龄的增长基因组损伤的发生实际上仍保持了小鼠造血干细胞（HSC）的储备。有证据表明，这是HSC静止（G0）细胞周期状态的结果，导致检查点控制的减弱以及DNA修复或凋亡的损伤反应。但是，在压力或组织再生的条件下，将已受到损伤的衰老干细胞召入循环时，其功能已严重受损。这些数据表明，年龄依赖性DNA损伤的积累可能是衰老的干细胞在急性应激或损伤后介导恢复稳态的能力下降的基础。此外，在无压力的稳态条件下，干细胞静止提供的细胞保护作用表明了一种机制，通过该机制，潜在的危险性损伤会随着年龄的增长而积累在干细胞池中。

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