Mitochondrial Dysfunction as a Cause of Aging

Mitochondrial dysfunction was implicated in the ageing process, with age-related accumulation of somatic mitochondrial DNA (mtDNA) mutations and decline in respiratory chain function observed in mammals. This dysfunction affected only a subset of cells in tissues like the heart, skeletal muscle, colonic crypts, and neurons. Studies on mtDNA mutator mice demonstrated that increased somatic mtDNA mutations could directly cause ageing phenotypes such as osteoporosis, hair loss, greying hair, weight reduction, and decreased fertility. Although mitochondrial dysfunction was often linked to increased reactive oxygen species (ROS) generation, experimental evidence for this was weak, as mice with mtDNA mutations showed little to no increase in oxidative stress. While mitochondrial dysfunction was clearly involved in human ageing, its overall significance in mammalian ageing was yet to be fully determined.