25. Cancer Is an Age-Associated Disease with an Added Layer of Clonal Selection

At the organismal level, cancer is a prominent age-associated disease, because the probability of localized malignancy rises as the deleteriome accumulates and protective functions degrade, making it easier for aberrant clones to appear and persist (53). What makes cancer mechanistically distinctive, relative to most other age-related diseases, is clonal selection. In addition to deleteriome components (e.g., passenger mutations), cancer has driver mutations that confer selective growth advantage within a given tissue context. As a result, damage may be diluted, and the cancer may be biologically younger than the host (but also may be older in some cases). Aging supplies the enabling landscape (more opportunities and a more permissive microenvironment), while selection supplies the amplification. Accordingly, cancer can be viewed as aging combined with evolution within the body. Consistently, adult tissues in older individuals often become mosaics of expanded mutant clones without overt malignancy, and cancer incidence diminishes in very old people as clones are unable to grow. A useful corollary is that aging has no discrete, designated drivers analogous to cancer drivers, and some longevity interventions may need parallel cancer-control strategies, especially when they increase proliferation, regeneration, or loosen differentiation constraints.