Abstract/Introduction
Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly higher amount of γH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared to young cells, and bone marrow failure in animals devoid of DNA repair factors. Novel data on the increase and the nature of DNA mutations in the hematopoietic system upon aging, the quality of the DNA damage response in aged HSCs and the nature of γH2AX foci question a direct link between DNA damage and the DNA damage response and aging of HSCs, and rather favor changes in epigenetics, splicing-factors or 3D architecture of the cell as major cell intrinsic factors of HSCs aging. Aging if HSCs is also driven by a strong contribution of aging of the niche. This review discusses the DNA damage theory of HSCs aging in the light of these novel mechanisms of aging of HSCs.