Ageing of bone marrow haematopoietic stem cells has been mostly associated with cell‐intrinsic mechanisms. New findings published in The EMBO Journal now show that reduced levels of the secreted matrix protein osteopontin in old bone marrow stroma cause ageing‐associated features in HSCs. In line, old HSCs are functionally rejuvenated by interaction with protease‐cleaved osteopontin fragment, and perform like young blood stem cells in vivo.
See also: N Guidi et al
As we age, the haematopoietic system undergoes significant changes that negatively impact our health. The incidence of anaemia and myeloid malignancy increase with age whereas adaptive immunity declines. Many of these perturbations can be traced back to alterations in haematopoietic stem cell (HSC) function. The bone marrow of elderly individuals contains an expanded HSC compartment, but the regenerative ability of these stem cells is impaired. Moreover, aged HSCs are biased towards myeloid differentiation at the expense of lymphoid cell production (Pang et al, 2017). As of yet, the molecular underpinnings of the age‐related decline in haematopoiesis have not been fully elucidated.
In the past, the ageing phenotype of HSCs was primarily attributed to cell‐intrinsic defects. Accordingly, old HSCs display unique transcriptional and epigenetic landscapes, suggestive of a molecular hardwiring of the ageing process (Janzen et al, 2006; Chambers et al, 2007). Defects in DNA repair and cell polarity are other features associated with ageing HSC proposed to represent cell‐autonomous mechanisms (Rossi et al …
Subscribers, please sign in with your username and password.