The ageing human and murine haematopoietic systems experience a well-documented age-dependent functional decline of stem cells due to cell-autonomous and microenvironmental (niche) factors9. These haematopoietic system changes coincide with alterations across all blood effector lineages. There is decreased competence in the innate immune system (decreased natural-killer activity, decreased phagocytic ability of neutrophils and macrophages, and a pro-inflammatory state) and the adaptive immune system (decreased numbers of naive B and T cells, and increased numbers of memory B and T cells), as well as expansion of the myeloid lineage and mild to moderate normocytic anaemia11. Most notably, retrospective analysis of bone marrow transplantations in patients has established that donor age is the only parameter significantly associated with survival of the transplant recipients, and this evidence is consistent with a cell-autonomous compromise in the function of haematopoietic stem cells (HSCs) from aged donors12. Importantly, these observations in ageing humans are supported by studies in ageing mice that clearly document a decrease in the number of functionally competent HSCs, as well as a preferred differentiation towards myeloid lineages over lymphoid lineages through a cell-autonomous process9.
