Guachalla 2009 Aging (Albany NY)
|Guachalla LM, Ju Z, Koziel R, Figura G, Song Z, Fusser M, Epe B, Jansen-Dürr P, Rudolph KL (2009) SOD2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice. Aging (Albany NY) 1:303-15.|
Abstract: Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidenceindicate 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.
• Keywords: Oxidative stress, Superoxide, Telomere shortening, Aging, DNA damage, SOD2, Free radicals, Stem cells
• O2k-Network Lab: AT Innsbruck Jansen-Duerr P
Labels: MiParea: Respiration, Genetic knockout;overexpression Pathology: Aging;senescence
Organism: Mouse Tissue;cell: Nervous system Preparation: Intact cells Enzyme: Uncoupling protein Regulation: Inhibitor, Redox state Coupling state: ROUTINE