Clonal hematopoiesis is linked to frailty in human cohorts

In an observational preprint examining 730,088 human participants from the UK Biobank, All of Us, BioVU, and the Women's Health Initiative, researchers evaluated whether somatic blood mutations track with frailty. Clonal hematopoiesis of indeterminate potential (CHIP) and autosomal mosaic chromosomal alterations showed strong associations with incident frailty and faster progression. These associations remained consistent across survey-based, directly measured, and clinically assessed frailty phenotypes. In contrast, mosaic loss of chromosome X or Y did not show an association. In humans, T-cell activation-related proteins mediated the link between clonal hematopoiesis and frailty. In parallel experiments, a Tet2 mouse model showed multisystem frailty-like functional decline alongside T-cell remodeling, supporting a model where clonal hematopoiesis accelerates biological aging through immunosenescence.