In summary, studies derived mainly from animal models but also from corroborating human correlative studies have demonstrated that stem cells of different organs show compromised proliferative and differentiation potential with advancing age and that this may not be reflected in a decrease in their numbers. This functional decline parallels compromised organ function, inadequate physiological responsiveness under stress and increased incidence of disease. Mechanistically, a wide range of genetic factors and pathways seem to contribute to the ageing process through their regulation of stem-cell and mitochondrial function. It is particularly notable that many of these genetic factors connect one way or another to genotoxic stress and the response to such DNA damage, as we discuss below.
