The integration of mitochondria into this core ‘axis of ageing’ is supported by the premature ageing conditions shared by telomere-dysfunctional or hyper-p53 mice, as well as mice that have excessive mitochondrial DNA mutation or are deficient in PGC-1α or PGC-1β, which are the master regulators of mitochondrial biogenesis and metabo-lism88–90, although the precise molecular basis for this commonality in premature ageing phenotypes remains to be elucidated. The marked decline in the function of largely post-mitotic organs in the telomer-ase knockout mouse prompts us to speculate that activated p53 may result in a decline in mitochondrial biogenesis and/or function through mechanisms that are as yet unknown. The identification of the specific molecular components and mechanisms linking p53 and mitochondrial dysfunction would provide a unifying basis for a central axis of ageing, linking genotoxic stress to stem-cell compromise, mitochondrial decline and, ultimately, 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
