title: Regulation of hematopoietic stem cell aging in vivo by a distinct genetic element.
abstract: Until recently, stem cells were thought to be endowed with unlimited self-renewal capacity and, thus, assumed exempt from aging. But accumulating evidence over the past decade compellingly argues that a measurable and progressive replicative impairment in the hematopoietic, intestinal, and muscle stem cell activity exists from adulthood to old age, resulting in a decline in stem cell function and rendering stem cell aging as the possible link between cellular aging and organismal aging. By using a previously uncharacterized congenic animal model to study genetic regulation of hematopoietic stem cell aging, we have demonstrated definitively that a locus on murine chromosome 2 regulates hematopoietic stem cell aging. In addition to demonstrating that hematopoietic stem cell aging is regulated by a distinct genetic element, experimental evidence links the response of hematopoietic stem cells to DNA double-strand breaks to cellular aging, suggesting DNA integrity influences stem cell aging.
authors.affiliation: Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. hartmut.geiger@cchmc.org
authors.forename: Hartmut
authors.initials: H
authors.lastname: Geiger
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rennebeck
authors.forename: Gary
authors.initials: G
authors.lastname: Van Zant
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D016026:Bone Marrow Transplantation; D016922:Cellular Senescence / Q000235:genetics*; D002874:Chromosome Mapping; D004249:DNA Damage; D005260:Female; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008954:Models, Biological; D014184:Transplantation, Homologous