Longevity & AgingSleep and exercise selectively rein in mutant blood stem cells and protect arteries
Clonal haematopoiesis (CH) is an age-related condition in which blood stem cells acquire mutations, expand, and raise atherosclerosis risk. This study asked whether lifestyle changes the course of CH. In two large human cohorts (UK Biobank and All of Us), more daily moderate-to-vigorous activity was linked to lower prevalence of non-DNMT3A CH, but not DNMT3A CH. In atherogenic mice, uninterrupted sleep and exercise slowed expansion of Jak2V617F and Tet2-deficient clones, while sleep fragmentation sped it up. Trp53 and Dnmt3aR878H clones did not respond in terms of expansion. Lifestyle selectively reprogrammed mutant cells, not neighbouring normal cells, through IL-1β signalling, CLEC4E inflammasome activity and noradrenaline-ADRβ2 signalling in vascular macrophages. The mouse findings are mechanistic, and the human data are associational.
