In mammals, species lifespan can vary by more than 100 fold (shrew 2 years, bowhead whale 211 years). Despite considerable research, the cellular mechanisms that make this variation possible remain unclear. In regard to these mechanisms, several predictions can be made. First, they must impact fundamental biochemical processes. Second, they would be expected to be related to structural differences between species at the cellular level. Furthermore, the goal would be to find significant correlation between cellular differences and the life span magnitude. As a tool to investigate these mechanisms, we have developed a series of skin fibroblast cell lines derived from mammalian species with a wide variation in lifespan (man, cow, bat, dog, mouse etc.). Using these lines, we have previously shown that the reported dependence of replicative capacity on longevity1 is most likely due to the dependence of replicative capacity on body mass, which is itself correlated with longevity2. Therefore, comparative studies of longevity must address the influence of body mass. The fact that DNA-PKcs and Ku 80 ablation in mice reduces average lifespan approximately 25% and 50% respectively and that Ku 80 null mice display symptoms of premature aging supports the potential role of these nuclear proteins in the aging process. DNA-PKcs and Ku are key proteins in double strand damage recognition. So we tested the capacity of skin fibroblast nuclear extracts from different mammalian species to bind DNA double strand breaks using an electrophoresis super-shift method that we have previously developed and that is now widely used in the field of DNA damage/repair3. Our results indicate that Ku-dependant DNA double strand break recognition increases exponentially with longevity and suggest that an enhanced ability to detect critical DNA damage may be a key requirement for longevity.

A. Lorenzini, A. Oliver, M. Tresini, V.J. Cristofalo, M. Malaguti, P. Biagi, et al. (2008). Is DNA double strand breaks recognition related to longevity?. FIRENZE : Firenze University Press.

Is DNA double strand breaks recognition related to longevity?

LORENZINI, ANTONELLO;MALAGUTI, MARCO;BIAGI, PIERLUIGI;HRELIA, SILVANA;
2008

Abstract

In mammals, species lifespan can vary by more than 100 fold (shrew 2 years, bowhead whale 211 years). Despite considerable research, the cellular mechanisms that make this variation possible remain unclear. In regard to these mechanisms, several predictions can be made. First, they must impact fundamental biochemical processes. Second, they would be expected to be related to structural differences between species at the cellular level. Furthermore, the goal would be to find significant correlation between cellular differences and the life span magnitude. As a tool to investigate these mechanisms, we have developed a series of skin fibroblast cell lines derived from mammalian species with a wide variation in lifespan (man, cow, bat, dog, mouse etc.). Using these lines, we have previously shown that the reported dependence of replicative capacity on longevity1 is most likely due to the dependence of replicative capacity on body mass, which is itself correlated with longevity2. Therefore, comparative studies of longevity must address the influence of body mass. The fact that DNA-PKcs and Ku 80 ablation in mice reduces average lifespan approximately 25% and 50% respectively and that Ku 80 null mice display symptoms of premature aging supports the potential role of these nuclear proteins in the aging process. DNA-PKcs and Ku are key proteins in double strand damage recognition. So we tested the capacity of skin fibroblast nuclear extracts from different mammalian species to bind DNA double strand breaks using an electrophoresis super-shift method that we have previously developed and that is now widely used in the field of DNA damage/repair3. Our results indicate that Ku-dependant DNA double strand break recognition increases exponentially with longevity and suggest that an enhanced ability to detect critical DNA damage may be a key requirement for longevity.
2008
Proceedings e report.53rd National Meeting of theItalian Society of Biochemistryand Molecular Biology(SIB)andNational Meeting of Chemistry of Biological SystemsItalian Chemical Society(SCI - Section CSB)
86
86
A. Lorenzini, A. Oliver, M. Tresini, V.J. Cristofalo, M. Malaguti, P. Biagi, et al. (2008). Is DNA double strand breaks recognition related to longevity?. FIRENZE : Firenze University Press.
A. Lorenzini; A. Oliver; M. Tresini; V.J. Cristofalo; M. Malaguti; P. Biagi; S. Hrelia; T.D. Stamato
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/98349
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