The DOI matches its Crossref record; 106 of the 106 references it cites were found in a registry or an index.
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 (37, 249).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [37]
In the citing paper
“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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Self-citationResveratrol improves health and survival of mice on a high-calorie diet
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Autophagy regulates lipid metabolism
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Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., et al. (2003) · Nature · doi:10.1038/nature01960 · Cited by 3,796
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy
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The Beclin 1 network regulates autophagy and apoptosis
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Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Colman, R. J., Anderson, R. M., Johnson, S. C., Kastman, E. K., Kosmatka, K. J., Beasley, T. M., Allison, D. B., Cruzen, C., Simmons, H. A., Kemnitz, J. W., et al. (2009) · Science · doi:10.1126/science.1173635 · Cited by 2,277
Autophagosome formation: core machinery and adaptations
Xie, Z., & Klionsky, D. J. (2007) · Nature Cell Biology · doi:10.1038/ncb1007-1102 · Cited by 2,237
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Self-citation
Research works printed but not linked: 3
- Willcox, 2014, Curr Opin Clin Nutr Metab Care., 17, 51
- Nicoli, 2014, Rom J Morphol Embryol., 55, 57
- Zhang, 2014, Autophagy., 10, 22
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Sarcopenia: Aging-Related Loss of Muscle Mass and Function
Larsson, L., Degens, H., Li, M., Salviati, L., Lee, Y. I., Thompson, W., Kirkland, J. L., & Sandri, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00061.2017 · Cited by 1,797
Autophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585
Self-citationHallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States
Mattson, M. P., & Arumugam, T. V. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.011 · Cited by 1,242
Cardioprotection and lifespan extension by the natural polyamine spermidine
Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., Pendl, T., Harger, A., Schipke, J., Zimmermann, A., Schmidt, A., et al. (2016) · Nature Medicine · doi:10.1038/nm.4222 · Cited by 1,168
Self-citationKaushik, S., & Cuervo, A. M. (2015) · Nature Medicine · doi:10.1038/nm.4001 · Cited by 899
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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