Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

被引:18
作者
Guachalla, Luis Miguel [1 ,2 ,3 ]
Ju, Zhenyu [1 ,2 ,6 ,7 ]
Koziel, Rafal [4 ]
von Figura, Guido [1 ,2 ,5 ]
Song, Zhangfa [1 ,2 ]
Fusser, Markus [8 ]
Epe, Bernd [8 ]
Jansen-Duerr, Pidder [4 ]
Rudolph, K. Lenhard [1 ,2 ]
机构
[1] Univ Ulm, Inst Mol Med, D-89081 Ulm, Germany
[2] Univ Ulm, Max Planck Res Grp Stem Cell Aging, D-89081 Ulm, Germany
[3] Int MD PhD Program, Hannover Med Sch, Hannover, Germany
[4] Austrian Acad Sci, Inst Biomed Aging Res, A-6020 Innsbruck, Austria
[5] Univ Ulm, Dept Internal Med 1, D-89081 Ulm, Germany
[6] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100037, Peoples R China
[7] Chinese Acad Med Sci, Max Planck Partner Grp Stem Cell Aging, Beijing 100037, Peoples R China
[8] Johannes Gutenberg Univ Mainz, Inst Pharm, D-55099 Mainz, Germany
来源
AGING-US | 2009年 / 1卷 / 03期
关键词
oxidative stress; superoxide; telomere shortening; aging; DNA damage; SOD2; free radicals; stem cells; MANGANESE SUPEROXIDE-DISMUTASE; MITOCHONDRIAL OXIDATIVE STRESS; NUCLEOTIDE EXCISION-REPAIR; REPLICATIVE LIFE-SPAN; DNA-BASE DAMAGE; CELLULAR SENESCENCE; MAMMALIAN-CELLS; REACTIVE OXYGEN; DEFICIENT MICE; KNOCKOUT MICE;
D O I
10.18632/aging.100030
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:303 / 315
页数:13
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