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oai:repisalud.isciii.es:20.500.12105/262122025-12-18T12:56:28Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Herranz, Daniel author Muñoz-Martin, Maribel author Cañamero, Marta author Mulero, Francisca author Martinez-Pastor, Barbara author Fernandez-Capetillo, Oscar author Serrano, Manuel author 2010-04-12 Genetic overexpression of protein deacetylase Sir2 increases longevity in a variety of lower organisms, and this has prompted interest in the effects of its closest mammalian homologue, Sirt1, on ageing and cancer. We have generated transgenic mice moderately overexpressing Sirt1 under its own regulatory elements (Sirt1-tg). Old Sirt1-tg mice present lower levels of DNA damage, decreased expression of the ageing-associated gene p16(Ink4a), a better general health and fewer spontaneous carcinomas and sarcomas. These effects, however, were not sufficiently potent to affect longevity. To further extend these observations, we developed a metabolic syndrome-associated liver cancer model in which wild-type mice develop multiple carcinomas. Sirt1-tg mice show a reduced susceptibility to liver cancer and exhibit improved hepatic protection from both DNA damage and metabolic damage. Together, these results provide direct proof of the anti-ageing activity of Sirt1 in mammals and of its tumour suppression activity in ageing- and metabolic syndrome-associated cancer. Nat Commun . 2010 Apr 12:1:3. Nature Communications 20975665 https://hdl.handle.net/20.500.12105/26212 SMALL-MOLECULE ACTIVATORS CALORIC RESTRICTION LIFE-SPAN RESVERATROLS TUMORIGENESIS SURVIVAL MICE EXPRESSION SIRTUIN DIET Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer.