SOD2

SOD2 is an antioxidant, the mitochondrial form of SOD and an important defence against oxidative damage. Evidence from invertebrates suggests it may play a role in ageing. Overexpression of SOD2 in flies significantly extends lifespan. Mice without SOD2 are not viable. Reducing the activity of SOD2 in mice increases the levels of oxidative damage to DNA but does not affect lifespan. SOD2 overexpression in mice slightly increases lifespan, while gene deletion in connective tissue only resulted in mutant mice with a reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis, osteoporosis and muscle degeneration. Loss of SOD2 activity in the epidermis induces cellular senescence. In the long-lived alphaMUPA mice strain, a reduced level of SOD2 gene expression and activity is observed together with maintaining the capacity to produce high levels of SOD2 in response to the inflammatory stimulus. Exercise training elevates levels of SOD2 in aging mouse hearts. Overexpression of SOD2 in aging mouse hearts demonstrated a protective role against oxidative stress, fibrosis and apoptosis. Surprisingly, young mice with epidermal SOD2 deficiency have accelerated wound closure. In contrast, old mice with epidermal SOD2 deficiency show delayed wound closure, reduced epidermal thickness and epidermal stem cell exhaustion. Polymorphisms in the human SOD2 gene have been associated with type 2 diabetes and cardiomyopathy. A longevity-associated polymorphism was observed for Ashkenazi males, but not for Italian and Jordanian populations. Although it is possible that SOD2 plays a role in human ageing, further studies are needed to investigate this hypothesis.