Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer

• Published in: Nature communications Vol. 1; no. 1; p. 3
• Main Authors: Herranz, Daniel, Muñoz-Martin, Maribel, Cañamero, Marta, Mulero, Francisca, Martinez-Pastor, Barbara, Fernandez-Capetillo, Oscar, Serrano, Manuel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.04.2010; Nature Publishing Group
• Subjects: 631/208/2489/68; 631/337; 631/443/7; 692/699/67/1504/1610; Aging; Aging - genetics; Aging - physiology; Animals; Cancer research; Deoxyribonucleic acid; Dietary Fats - adverse effects; Diethylnitrosamine - toxicity; DNA; DNA damage; DNA Damage - genetics; DNA Damage - physiology; Female; Glucose Tolerance Test; Humanities and Social Sciences; Liver cancer; Liver Neoplasms - etiology; Liver Neoplasms - therapy; Longevity; Longevity - genetics; Longevity - physiology; Lymphoma; Male; Mammals; Medical research; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - complications; Metabolic Syndrome - therapy; Mice; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Neoplasms - etiology; Neoplasms - metabolism; Proteins; Research centers; Sarcoma; Science; Science (multidisciplinary); Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Transgenic animals; Tumors; Spain
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1001

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. Ageing associated diseases are the subject of intense study. In this article Serrano and colleagues demonstrate that Sirt1 over-expression in mice prevents both ageing associated diseases and liver cancer.