Oxidative stress and telomere attrition are considered the driving factors of aging. As oxidative damage to telomeric DNA favors the erosion of chromosome ends and, in turn, telomere shortening increases the sensitivity to pro-oxidants, these two factors may trigger a detrimental vicious cycle. To check whether limiting oxidative stress slows down telomere shortening and related progeria, we have investigated the effect of p66SHC deletion, which has been shown to reduce oxidative stress and mitochondrial apoptosis, on late-generation TERC (telomerase RNA component)-deficient mice having short telomeres and reduced lifespan. Double mutant (TERC-/- p66SHC-/-) mice were generated, and their telomere length, fertility, and lifespan investigated in different generations. Results revealed that p66SHC deletion partially rescues sterility and weight loss, as well as organ atrophy, of TERC-deficient mice, but not their short lifespan and telomere erosion. Therefore, our data suggest that p66SHC-mediated oxidative stress and telomere shortening synergize in some tissues (including testes) to accelerate aging; however, early mortality of late-generation mice seems to be independent of any link between p66SHC-mediated oxidative stress and telomere attrition.

P66SHC deletion improves fertility and progeric phenotype of late-generation TERC-deficient mice but not their short lifespan / M. Giorgio, M. Stendardo, E. Migliaccio, P.G. Pelicci. - In: AGING CELL. - ISSN 1474-9718. - 15:3(2016 Jun), pp. 446-454. [10.1111/acel.12448]

P66SHC deletion improves fertility and progeric phenotype of late-generation TERC-deficient mice but not their short lifespan

P.G. Pelicci
Ultimo
2016

Abstract

Oxidative stress and telomere attrition are considered the driving factors of aging. As oxidative damage to telomeric DNA favors the erosion of chromosome ends and, in turn, telomere shortening increases the sensitivity to pro-oxidants, these two factors may trigger a detrimental vicious cycle. To check whether limiting oxidative stress slows down telomere shortening and related progeria, we have investigated the effect of p66SHC deletion, which has been shown to reduce oxidative stress and mitochondrial apoptosis, on late-generation TERC (telomerase RNA component)-deficient mice having short telomeres and reduced lifespan. Double mutant (TERC-/- p66SHC-/-) mice were generated, and their telomere length, fertility, and lifespan investigated in different generations. Results revealed that p66SHC deletion partially rescues sterility and weight loss, as well as organ atrophy, of TERC-deficient mice, but not their short lifespan and telomere erosion. Therefore, our data suggest that p66SHC-mediated oxidative stress and telomere shortening synergize in some tissues (including testes) to accelerate aging; however, early mortality of late-generation mice seems to be independent of any link between p66SHC-mediated oxidative stress and telomere attrition.
fertility; lifespan; oxidative DNA damage; telo-meres; cell biology; aging
Settore MED/04 - Patologia Generale
giu-2016
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/425011
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