1 research outputs found
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