Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
Open accessAbstract
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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SIRT1 protects against ageing-associated metabolic diseases such as glucose intolerance and cancer.
“As such, SIRT1 confers protection against ageing-associated metabolic diseases such as glucose intolerance and cancer (Herranz et al., 2010; Pearson et al., 2008; Rutanen et al., 2010).”
From Calorie Restriction-like Effects of 30 Days of Resveratrol Supplementation on Energy Metabolism and Metabolic Profile in Obese Humans (2011) · cites this paper as Herranz et al., 2010
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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)
- PMC
- PMC3641391
- 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
- bronze
- doi.org
- Licence
- 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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