Life-long reduction in MnSOD activity leads to increased levels of oxidative DNA damage and increase cancer incidience, but does not appear to affect aging. Sod2(+/-) mice that have a 50% reduction in MnSOD activity in all tissues throughout the life have increased oxidative damage as evidenced by significantly elevated levels of 8-oxo-2-deoxyguanosine in nuclear DNA (in all tissues) as well as in mitochondrial DNA (in lver and brain). Increased oxidative damage to DNA is associated with a 100% increase in tumor incidience in old Sod2(+/-) mice. However, mean and maximum lifespan of Sod2(+/-) and wild-type mice is identical. Biomarkers of aging, such as catarct formation, immune response, and formation of glycooxidation products carboxylmethyl lysine and pentosidine in skin collagen changes with age to the same extent in both wild-type and Sod2(+/-) mice.
Sod2(+/-);Gpx(-/-) animals exhibit no reduction in lifespan, despite increased levels of oxidative damage and neoplasms as well as tumorgenesis [19776219].
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