Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue

被引：86

作者：

Treiber, Nicolai ^{[1
]}

Maity, Pallab ^{[1
]}

Singh, Karmveer ^{[1
]}

Kohn, Matthias ^{[1
]}

Keist, Alexander F. ^{[1
]}

Ferchiu, Florentina ^{[1
]}

Sante, Lea ^{[1
]}

Frese, Sebastian ^{[2
]}

Bloch, Wilhelm ^{[2
]}

Kreppel, Florian ^{[3
]}

Kochanek, Stefan ^{[3
]}

Sindrilaru, Anca ^{[1
]}

Iben, Sebastian ^{[1
]}

Hoegel, Josef ^{[4
]}

Ohnmacht, Michael ^{[5
]}

Claes, Lutz E. ^{[5
]}

Ignatius, Anita ^{[5
]}

Chung, Jin H. ^{[6
]}

Lee, Min J. ^{[6
]}

Kamenisch, York ^{[7
]}

Berneburg, Mark ^{[7
]}

Nikolaus, Thorsten ^{[8
]}

Braunstein, Kerstin ^{[9
]}

Sperfeld, Anne-Dorte ^{[9
]}

Ludolph, Albert C. ^{[8
,9
]}

Briviba, Karlis ^{[10
]}

Wlaschek, Meinhard ^{[1
]}

Scharffetter-Kochanek, Karin ^{[1
,8
]}

机构：

[1] Univ Ulm, Dept Dermatol & Allerg Dis, D-89081 Ulm, Germany

[2] German Sports Univ, Dept Mol & Cellular Sports Med, D-50927 Cologne, Germany

[3] Univ Ulm, Div Gene Therapy, Dept Mol Med, D-89081 Ulm, Germany

[4] Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany

[5] Univ Ulm, Inst Orthopaed Res & Biomech, D-89081 Ulm, Germany

[6] Seoul Natl Univ Hosp, Dept Dermatol, Seoul 110744, South Korea

[7] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany

[8] Competence Ctr Gerontol & Aging Res, D-89081 Ulm, Germany

[9] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany

[10] Fed Res Ctr Nutr & Food, Inst Nutr Physiol, D-76131 Karlsruhe, Germany

来源：

AGING CELL | 2011年 / 10卷 / 02期

关键词：

Aging; connective tissue; mitochondria; p16INK4a; reactive oxygen species; Sod2; SKELETAL-MUSCLE MASS; DNA MUTATIONS; BONE MASS; FIBROBLASTS; SARCOPENIA; DAMAGE; GENERATION; EXPRESSION; REDUCTION; CANCER;

D O I：

10.1111/j.1474-9726.2010.00658.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

P>The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchyme-derived cells of connective tissues in all organs. Here, we have shown for the first time that the connective tissue-specific lack of superoxide anion detoxification in the mitochondria results in reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis and muscle degeneration in mutant mice. Increase in p16INK4a, a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype. This novel model is particularly suited to decipher the underlying mechanisms and to develop hopefully novel connective tissue-specific anti-aging strategies.

引用

页码：239 / 254

页数：16

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