Cited by 612Sirtuins and Resveratrol in MedicineGenetics, Aging, and Longevity in Model OrganismsMetabolism, Diabetes, and Cancer

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

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Herranz, Daniel, Muñoz-Martin, Maribel, Cañamero, Marta, Mulero, Francisca, Martinez-Pastor, Barbara, Fernandez-Capetillo, Oscar, Serrano, Manuel·2010·Nature Communications

Abstract

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.

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Authors
Herranz, D., Muñoz-Martin, M., Cañamero, M., Mulero, F., Martinez-Pastor, B., Fernandez-Capetillo, O., & Serrano, M.
Affiliations
Spanish National Cancer Research Centre (ES)
Corresponding author
Serrano, Manuel
Venue
Nature Communications
Published
2010-04-12
Volume
1
Issue
1
Pages
3-3
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2082431118
Cited by
612
References
42
Citations by year
2026: 11 · 2025: 19 · 2024: 20 · 2023: 21 · 2022: 33 · 2021: 43 · 2020: 33 · 2019: 43 · 2018: 40 · 2017: 45 · 2016: 57 · 2015: 50 · 2014: 53 · 2013: 63 · 2012: 44
FWCI
18.43
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
SIRT1, Sir2, healthy aging, liver cancer, tumor suppression, DNA damage, p16INK4a, longevity, transgenic mice, hepatoprotection, metabolic damage
MeSH terms
Aging, Animals, Dietary Fats, Diethylnitrosamine, DNA Damage, Female, Glucose Tolerance Test, Liver Neoplasms, Longevity, Male, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Metabolic Syndrome, Mice, Sirtuin 1

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