organ atrophy, functional decline and the diminished energy production that typifies essentially all aspects of cellular and physiological decline in ageing organisms. Indeed, this mitochondrial perspective gains added appeal when one considers that a hallmark feature of ageing is generalized frailty, which may derive from a fundamental inability to produce adequate levels of cellular ATP. This genotoxic stress model of ageing emphasizes the need to develop a better understanding of the factors that influence telomere erosion, the genes that protect cells against ROS-induced damage, the signals that regulate p53 activity and the pathways that maintain mitochondrial reserves and function. It remains to be established how these various pathways are differentially activated during ageing and how they might be interconnected. Deciphering these networks could yield ageing biomarkers and advance therapeutic strategies (including stabilization of telomeres through transient telomerase reactivation, p53 modulation, improvement in mitochondrial function and biogenesis, and modulation of the mTOR and PI(3)K pathways) designed to rejuvenate both proliferating and quiescent tissues in the aged.
