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Trends Mol Med. 2016 Aug;22(8):701-712. doi: 10.1016/j.molmed.2016.06.003. Epub 2016 Jul 2.

Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.

Author information

1
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229, USA. Electronic address: Shailaja.Akunuru@cchmc.org.
2
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229, USA; Institute for Molecular Medicine, Ulm University, 89081 Ulm, Germany; aging research center, Ulm University, 89081 Ulm, Germany. Electronic address: hartmut.geiger@cchmc.org.

Abstract

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.

PMID:
27380967
PMCID:
PMC4969095
DOI:
10.1016/j.molmed.2016.06.003
[Indexed for MEDLINE]
Free PMC Article

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