An open access commentary at Impact Aging: "There is a lively discussion going on as to whether oxidative stress is or is not a cause of (accelerated) aging, fuelled to a significant extent by the finding from Arlan Richardson's group that mice heterozygous for the mitochondrial superoxide dismutase SOD2 showed increased oxidative stress, increased cancer incidence but not accelerated ageing. A new twist to this story was introduced recently when it was shown that connective tissue-specific SOD2 knockouts developed multiple signs of progeria including short lifespan, associated with up-regulation of the cell senescence marker p16INK4A. Mitochondrially generated oxidative stress is both an established cause and a relevant consequence of cell senescence, frequencies of senescent cells in connective tissue increase during mice aging, and destruction of senescent cells can 'cure' some age-related tissue dysfunction. A paper by Judith Campisi's and Simon Melov's groups recently published in Aging now further explores the connection between oxidative stress, cell senescence and aging. The authors demonstrate that mitochondrial dysfunction occurs in the epidermis of old (2 years) mice ... These data enforce two central hypotheses in the field, namely that of mitochondrial dysfunction as a cause of cell senescence, and of cell senescence as a relevant contributor to mammalian aging ... However, a fascinating question remains: Is it really Reactive Oxygen Species (ROS) arising from mitochondria that promote cellular senescence in this model?"