p21 deletion rescues stem cell senescence and premature ageing of telomere dysfunctional mice without accelerating cancer formation

Introduction: Telomere shortening is associated with acceleration of ageing, chronic disease, and mortality in humans. Mutations that predispose to a failure to maintain telomere length induce a premature decline in organ homeostasis and a shortened lifespan in human and mice. Upon reaching a critically short length, dysfunctional telomeres activate the ATM/p53 DNA damage pathway and its downstream target p21, which induces a permanent G1 cell cycle arrest in primary human cells known as senescence. Aim: The functional role of p21-induced senescence in response to telomere dysfunction during organismal ageing in…