Changing prevalence spectra of CH driver genes with advancing age, and the clonal dynamics underpinning these changes. (A) DNMT3A mutations dominate the landscape of CH in younger individuals, but TET2 becomes the most prevalent driver gene in older people. Mutations in splicing factor genes and PPM1D also become more common in advanced old age. (B) Schematic illustration of gene-specific CH dynamics across the human lifespan. Typical trajectories are shown for each of 3 important CH drivers. DNMT3A-mutant clones preferentially expand early in life and display slower growth in old age; splicing gene mutations drive rapid expansion only later in life; TET2-mutant clones emerge across all ages and tend to drive moderate but stable rates of growth. Data for panel A were from Fabre et al.¹⁸