Naturally occurring p16 Ink4a -positive cells shorten healthy lifespan

0 0 M o n t h 2 0 1 6 | V o L 0 0 0 | n A t U R E | 1 Cellular senescence is a well-established cancer defence mechanism that has also been proposed to have roles in ageing and age-associated diseases, presumably through the depletion of stem and progenitor cells, and the adverse actions of the senescence-associated secretory phenotype, which consists of many proinflammatory cytokines and chemokines, matrix metalloproteinases and growth factors 1–3 . Consistent with this idea is the observation that interference with senescent cell accumulation in BubR1 progeroid mice delays several of the ageing-associated disorders that these animals develop 4,5 . However, because progeroid syndromes do not mimic the complex degenera-tive changes of ageing completely, the relevance of these findings has remained unclear. Furthermore, recent studies showing that senescent cells have beneficial effects in injury repair and tissue remodelling 6–10 have called into question the simplistic view of senescence as only a driver of age-dependent pathologies, raising the specter that senes-cent cell clearance might remove useful cells in addition to detrimental ones. Here we investigated the identity and physiological effect of nat-urally occurring senescent cells using INK-ATTAC (hereafter termed ATTAC) 4