title: Age-related changes in human hematopoietic stem/progenitor cells.
abstract: Adult stem cells are critical for maintaining cellular homeostasis throughout life, yet the effects of age on their regenerative capacity are poorly understood. All lymphoid and myeloid blood cell lineages are continuously generated from hematopoietic stem cells present in human bone marrow. With age, significant changes in the function and composition of mature blood cells are observed. In this study, we report that age-related changes also occur in the human hematopoietic stem cell compartment. We find that the proportion of multipotent CD34(+) CD38(-) cells increases in the bone marrow of elderly (>70 years) individuals. CD34(+) CD38(+) CD90(-) CD45RA(+/-) CD10(-) and CD34(+) CD33(+) myeloid progenitors persist at the same level in the bone marrow, while the frequency of early CD34(+) CD38(+) CD90(-) CD45RA(+) CD10(+) and committed CD34(+) CD19(+) B-lymphoid progenitors decreases with age. In contrast to mice models of aging, transplantation experiments with immunodeficient NOD/SCID/IL-2Rγ null (NSG) mice showed that the frequency of NSG repopulating cells does not change significantly with age, and there is a decrease in myeloid lineage reconstitution. An age-related decrease in the capacity of CD34(+) cells to generate myeloid cells was also seen in colony-forming assays in vitro. Thus, with increasing age, human hematopoietic stem/progenitor cells undergo quantitative changes as well as functional modifications.
authors.affiliation: INSERM UMRS, Paris, France.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Kuranda
authors.forename: Jacques
authors.initials: J
authors.lastname: Vargaftig
authors.forename: Philippe
authors.initials: P
authors.lastname: de la Rochere
authors.forename: Christine
authors.initials: C
authors.lastname: Dosquet
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Florence
authors.initials: F
authors.lastname: Bardin
authors.forename: Cecile
authors.initials: C
authors.lastname: Tonnelle
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
authors.forename: Michele
authors.initials: M
authors.lastname: Goodhardt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000818:Animals; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D015703:Antigens, CD