Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence-indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two-observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in-cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial-derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2(+/-)) would exacerbate aging-phenotypes in telomere dysfunctional (mTerc(-/-)) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein-levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal-levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere-shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the-impairment in organ maintenance in aging mTerc-/- mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc(-/-) mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction.