Somatic blood mutations associate with accelerated frailty and functional decline in humans

In a new preprint, researchers examined 730,088 human participants from the UK Biobank, All of Us, BioVU, and the Women's Health Initiative to study somatic mutations in the blood. They evaluated how these mutations affect incident frailty and functional decline across multiple organ systems. The team found that clonal hematopoiesis of indeterminate potential and autosomal mosaic chromosomal alterations were strongly associated with frailty and healthspan phenotypes. In contrast, mosaic loss of chromosome X or Y showed no link. In humans, T-cell activation-related proteins mediated the association between clonal hematopoiesis and frailty. Complementary tests in a Tet2 mouse model demonstrated multisystem frailty-like functional decline alongside T-cell remodeling. Together, the findings indicate that clonal hematopoiesis accelerates biological aging through immunosenescence.