Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.
Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.
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DOI：
10.1016/j.molmed.2016.06.003
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发表时间：
2016-08
影响因子：
13.6
通讯作者：
Geiger H
中科院分区：
文献类型：
--
作者：
Akunuru S;Geiger H
衰老与器官功能下降和疾病发病率增加有关。由细胞内在和外在因素驱动的造血干细胞 (HSC) 衰老与 HSC 自我更新和再生受损、衰老相关的免疫重塑以及白血病发病率增加有关。 DNA 损伤反应受损和活性氧产生增加此前已被认为是 HSC 衰老的原因。然而，最近的范式转变概念，例如全局表观遗传和细胞骨架极性转变、细胞衰老以及衰老时 HSC 的克隆选择，为 HSC 衰老机制提供了新的见解。可以重新编程衰老 HSC 表观遗传状态的再生剂或选择性消耗衰老细胞的抗衰老药物为减轻造血衰老并可能减轻与衰老相关的免疫重塑和骨髓恶性肿瘤提供了有希望的转化途径。
Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and increased production of reactive oxygen species have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as clonal selection of HSCs upon aging provide new insights into HSC aging mechanisms. Rejuvenating agents that can reprogram the epigenetic status of aged HSCs or senolytic drugs that selectively deplete senescent cells provide promising translational avenues for attenuating hematopoietic aging and potentially, alleviating aging-associated immune remodeling and myeloid malignancies.