Telomeres, senescence, oxidative stress, and heterogeneity

Life span heterogeneity is a hallmark of the ageing process. It is also a characteristic feature of telomere-dependent replicative senescence. We review here evidence showing that telomere shortening is heterogeneous between telomeres and between cells, and relate this to cell-to-cell variation in mitochondrial function and production of reactive oxygen species (ROS). Telomere shortening is to a large extent governed by ROS-mediated telomeric DNA damage, and we show here that apparently stochastic variation in mitochondrial ROS production can account for vast differences in replicative potential between individual cell lineages.