Hematopoietic stem cells (HSCs)

Haematopoietic stem cells (HSCs) are rare, multipotent progenitors residing primarily in the bone marrow that sustain lifelong blood cell production through asymmetric self-renewal divisions and hierarchical differentiation into all lymphoid and myeloid lineages. With ageing, the HSC pool expands numerically but deteriorates functionally: aged HSCs show myeloid-biased output at the expense of lymphopoiesis, reduced engraftment efficiency, increased DNA damage, altered epigenetic landscapes, and mitochondrial dysfunction. Clonal haematopoiesis — the age-associated expansion of HSC clones carrying somatic mutations in epigenetic regulators such as DNMT3A, TET2, and ASXL1 — is present in approximately 10% of individuals over 70 with conventional sequencing depth (and substantially more on deep sequencing) and confers elevated risk of haematological malignancy, cardiovascular disease, and all-cause mortality, establishing HSC ageing as a direct contributor to systemic health decline.