Journal
AGING CELL
Volume 10, Issue 2, Pages 239-254Publisher
WILEY
DOI: 10.1111/j.1474-9726.2010.00658.x
Keywords
Aging; connective tissue; mitochondria; p16INK4a; reactive oxygen species; Sod2
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Funding
- German Research Foundation within the Clinical Research Group [KFO142]
- European Union [FP6-518230]
- German Research Foundation within the Collaborative Research Centre [SFB 497]
- Korea Science and Engineering Foundation (KOSEF) through the Centre for Aging and Apoptosis Research at Seoul National University [R11-2002-097-06001-0]
- National Research Foundation of Korea [R11-2002-097-06001-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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