title: Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.
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.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229, USA. Electronic address: Shailaja.Akunuru@cchmc.org.
authors.forename: Shailaja
authors.initials: S
authors.lastname: Akunuru
authors.affiliation: 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.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Geiger
mesh_terms: D000375:Aging; D000818:Animals; D000066673:Cell Self Renewal; D016922:Cellular Senescence; D004249:DNA Damage; D044127:Epigenesis, Genetic; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species