Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells

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. Comp...

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Bibliographic Details
Published in:Trends in molecular medicine 2016-08, Vol.22 (8), p.701-712
Main Authors: Akunuru, Shailaja, Geiger, Hartmut
Format: Article
Language:English
Subjects:
Aging
Animals
Cell Self Renewal
Cellular Senescence
DNA Damage
Epigenesis, Genetic
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Humans
Pathology
Reactive Oxygen Species - metabolism
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Summary: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 the increased production of reactive oxygen species (ROS) 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 the 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.
ISSN:1471-4914
1471-499X
DOI:10.1016/j.molmed.2016.06.003