Fig. 7

Mechanism of HSC aging. HSCs undergo niche-driven and proliferation-associated changes during aging. Proliferation induces multiple stresses on HSCs including replication, ribosome biosynthesis, DNA damage, as well as metabolic and epigenetic stresses. Such stresses attenuate the self-renewal capacity of HSCs by inducing p53-dependent/independent senescence/apoptosis and promote lineage-biased differentiation by inducing platelet/myeloid genes and repressing lymphoid genes. Aging of HSC niches promotes the switch from asymmetric division to symmetric division in HSCs and impairs the self-renewal of HSCs due to a reduction in key niche factors including SCF, Cxcl12, IL7, and Notch ligands. In addition, the accumulation of MKs, M, plasma cells (PCs), aging-associated B cells, and MDSCs, which is primed by inflammatory mediators, promotes the Plt/My-biased phenotype in HSCs through the production of inflammatory cytokines such as CCL5, IL1β, TNFα, IFN-γ, Wnt5 and TGFβ