The life span-prolonging effect of Sirtuin-1 is mediated by autophagy
Open accessAbstract
The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life spanextending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.
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Functional macroautophagy is necessary to attain the maximal lifespan extension mediated by mutations in the nutrient-sensor TOR, the tumor suppressor protein p53, and the lifespan prolonging effect of Sirt-1.
“Functional macroautophagy has also proven necessary to attain the maximal lifespan extension mediated by mutations in other genes such as the nutrient-sensor TOR (Hansen et al., 2008), the tumor suppressor protein p53 (Tavernarakis et al., 2008) and even the lifespan prolonging effect of Sirt-1 (Morselli et al., 2010).”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Morselli et al., 2010
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Targeting the Mitochondria-Proteostasis Axis to Delay Aging
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- Authors
- Morselli, E., Maiuri, M. C., Markaki, M., Megalou, E., Pasparaki, A., Palikaras, K., Criollo, A., Galluzzi, L., Malik, S. A., Vitale, I., Michaud, M., Madeo, F., Tavernarakis, N., & Kroemer, G.
- Affiliations
- Inserm (FR)
- Université Paris-Sud (FR)
- Foundation for Research and Technology Hellas (GR)
- Instituto Nazionale Tumori Regina Elena (IT)
- University of Graz (AT)
- Corresponding author
- Tavernarakis, Nektarios
- Kroemer, Guido
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2010-01
- Volume
- 6
- Issue
- 1
- Pages
- 186-188
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2080956520
- Cited by
- 139
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 12 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 8 · 2016: 13 · 2015: 8 · 2014: 6 · 2013: 10 · 2012: 14
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Agence Nationale de la Recherche
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Institut National Du Cancer
- Institute of Cancer Research
- 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
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- SIRT1, lifespan extension, longevity, caloric restriction, resveratrol, nutrient deprivation, Caenorhabditis elegans, mTOR inhibition, p53, cancer cells, deacetylase
- MeSH terms
- Aging, Animals, Autophagy, Enzyme Activation, Humans, Models, Biological, Caenorhabditis elegans, Animals, Genetically Modified, Sirtuin 1
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