title: Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice.
abstract: 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.
authors.affiliation: Institute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Aging, University of Ulm, 89081 Ulm, Germany.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Guachalla
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ju
authors.forename: Rafal
authors.initials: R
authors.lastname: Koziel
authors.forename: Guido
authors.initials: G
authors.lastname: von Figura
authors.forename: Zhangfa
authors.initials: Z
authors.lastname: Song
authors.forename: Markus
authors.initials: M
authors.lastname: Fusser
authors.forename: Bernd
authors.initials: B
authors.lastname: Epe
authors.forename: Pidder
authors.initials: P
authors.lastname: Jansen-Durr
authors.forename: K Lenhard
authors.initials: KL
authors.lastname: Rudolph
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016922:Cellular Senescence; D004249:DNA Damage; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006579:Heterozygote; D008136:Longevity; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics; D019098:Telomerase / Q000172:deficiency / Q000235:genetics; D016615:Telomere / Q000378:metabolism / Q000473:pathology*; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D013482:Superoxide Dismutase; D019098:Telomerase; D000099156:Superoxide Dismutase 2