The aging of hematopoietic stem cells

Abstract

We have purified hematopoietic stem cells (HSCs) from the bone marrow of old mice and compared their properties to HSCs in young and middle-aged mice. Single, reconstituting HSCs (by limit dilution) from old and young mice exhibited indistinguishable progenitor activities in vivo. HSCs were five times as frequent in the bone marrow of old mice; however, HSCs from old mice were only one-quarter as efficient at homing to and engrafting the bone marrow of irradiated recipients. HSCs in young and middle-aged mice rarely were in the S/G2/M phases of the cell cycle, but HSCs in old mice were frequently in cycle. We speculate that the unexpected proliferation of HSCs in old mice might be related to the increased incidence of leukemia in old mice. HSCs change with age, but it is unknown whether these changes are determined intrinsically or caused by the aging of their environment.

Aging of hematopoietic stem cells is regulated by the stem cell niche

“…Competitive repopulation assays in murine transplantation models demonstrated that older bone marrow contains a higher number of repopulating HSC (2-3 fold higher) (Morrison et al, 1996). This is in line with similar in vitro experiments using the cobblestone area forming cell ( …”

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

“…Aging of HSCs was thought to be primarily regulated by cell intrinsic‐driven mechanisms (Morrison et al , 1996; Rossi et al , 2005; Chambers & Goodell, 2007; Geiger et al , 2013). In this study, we demonstrate a critical role for decreased OPN in osteoblasts in aged endosteal‐enriched stroma cells for inferring aging‐associated phenotypes on HSCs, while exposing old LT‐HSCs to OPN fragments activated by thrombin results in the attenuation of aging‐associated phenotypes and function of aged HSCs.…”

Epigenetic regulation of aging stem cells

“…HSCs isolated from older mice show defects in mobilization and homing to bone marrow (Morrison et al, 1996;Kim et al, 2003;Liang et al, 2005;Xing et al, 2006). In competitive transplantation assays, a rigorous test for both self-renewal and multipotency during which donor HSCs are co-injected with wild-type bone marrow and assessed for their ability to regenerate all blood lineages, aged HSCs shows defect in long-term reconstitution of the immune system (Sudo et al, 2000;Kamminga et al, 2005;Rossi et al, 2005;Chambers et al, 2007).…”