Essential role for autophagy in life span extension
Open accessAbstract
Life and health span can be prolonged by calorie limitation or by pharmacologic agents that mimic the effects of caloric restriction. Both starvation and the genetic inactivation of nutrient signaling converge on the induction of autophagy, a cytoplasmic recycling process that counteracts the age-associated accumulation of damaged organelles and proteins as it improves the metabolic fitness of cells. Here we review experimental findings indicating that inhibition of the major nutrient and growth-related signaling pathways as well as the upregulation of anti-aging pathways mediate life span extension via the induction of autophagy. Furthermore, we discuss mounting evidence suggesting that autophagy is not only necessary but, at least in some cases, also sufficient for increasing longevity.
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Because resveratrol activates mitochondrial biogenesis through the AMPK-SIRT1-PGC1α axis, it prompts mitochondrial biogenesis, the unfolded protein response, and autophagy machinery that are known to extend longevity in animals.
“Because resveratrol activates mitochondrial biogenesis through the AMPK-SIRT1-PGC1α axis, it prompts mitochondrial biogenesis, the unfolded protein response, and autophagy machinery that are known to extend longevity in animals (37, 249).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [37]
Many paradigms of life extension depend on autophagy in model organisms (yeast, Drosophila, Caenorhabditis elegans and mice).
“It has been shown in model organisms (yeast, Drosophila, Caenorhabditis elegans and mice) that many paradigms of life extension depend on autophagy [34,130,135,136].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [135]
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BackgroundMetformin as a geroprotector: experimental and clinical evidence
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- Authors
- Madeo, F., Zimmermann, A., Maiuri, M. C., & Kroemer, G.
- Affiliations
- University of Graz (AT)
- Inserm (FR)
- Corresponding author
- Madeo, Frank
- Zimmermann, Andreas
- Kroemer, Guido
- Venue
- Journal of Clinical Investigation
- Published
- 2015-01-02
- Volume
- 125
- Issue
- 1
- Pages
- 85-93
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4382258
- OpenAlex
- W2021632384
- Cited by
- 464
- References
- 106
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 18 · 2023: 27 · 2022: 31 · 2021: 54 · 2020: 45 · 2019: 53 · 2018: 60 · 2017: 55 · 2016: 44 · 2015: 18
- FWCI
- 5.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Austrian Science Fund (P 24381, I1000, P 23490)
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Fondation de France
- Institut National Du Cancer
- Institut Gustave-Roussy
- Karl-Franzens-Universität Graz
- Labex Immuno-Oncology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- autophagy, lifespan extension, longevity, caloric restriction, nutrient signaling, starvation, protein quality control, organelle recycling, growth factor signaling
- MeSH terms
- Acetylation, Animals, Autophagy, Humans, Longevity, Phagosomes, Protein Processing, Post-Translational, Paracrine Communication
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