The effects of p53 on whole organism longevity are mediated by autophagy
Open accessAbstract
The tumor suppressor protein p53 has a major impact on organismal aging. Recently it has become clear that p53 not only controls DNA damage responses, senescence and apoptosis but also plays a major role in the control of autophagy. Thus, deletion, depletion, or inhibition of p53 induces autophagy in human, mouse and nematode cells. We therefore tested the hypothesis that the mutation of the p53 orthologue CEP-1 might increase the life span of Caenorhabditis elegans through an increase in baseline autophagy. For this, we evaluated the survival of nematodes lacking cep-1, alone or in combination with RNA inference with the autophagy gene bec-1 (which encodes the orthologue of Atg6/Beclin 1). cep-1 mutants exhibited a prolonged life span. While BEC-1 depletion during adult life did not cause significant modification of the life expectancy of wild type controls, it did reduce the increased life span of cep-1 mutants down to approximately normal levels. These results indicate that the life span-extending effect of the cep-1 mutation is mediated by autophagy. These results lend support to the hypothesis that autophagy has a broad positive impact on organismal aging.
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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 Tavernarakis et al., 2008
Knocking down genes essential for autophagy abrogates lifespan extension in worms, arguing for a causal link between autophagy and longevity.
“The fact that knocking down genes essential for autophagy abrogates lifespan extension in worms (Jia and Levine, 2007; Tavernarakis et al., 2008) argues for a causal link between autophagy and longevity.”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Tavernarakis et al., 2008
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Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Self-citationAutophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452 · see citing works
Vousden, K. H., & Lane, D. P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2147 · Cited by 2,275 · see citing works
DRAM, a p53-Induced Modulator of Autophagy, Is Critical for Apoptosis
Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P. R., Gasco, M., Garrone, O., Crook, T., & Ryan, K. M. (2006) · Cell · doi:10.1016/j.cell.2006.05.034 · Cited by 1,380 · see citing works
Kamath, R. S., Martinez-Campos, M., Zipperlen, P., Fraser, A. G., & Ahringer, J. (2000) · Genome biology · doi:10.1186/gb-2000-2-1-research0002 · Cited by 1,315 · see citing works
Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in <i>C. elegans</i>
Meléndez, A., Tallóczy, Z., Seaman, M., Eskelinen, E.-L., Hall, D. H., & Levine, B. (2003) · Science · doi:10.1126/science.1087782 · Cited by 1,270 · see citing works
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235 · see citing works
Regulation of autophagy by cytoplasmic p53
Tasdemir, E., Maiuri, M. C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1730 · Cited by 1,132 · see citing works
Self-citationA Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans
Hansen, M., Chandra, A., Mitic, L. L., Onken, B., Driscoll, M., & Kenyon, C. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.0040024 · Cited by 766 · see citing works
Longevity pathways converge on autophagy genes to regulate life span inCaenorhabditis elegans
Tóth, M. L., Sigmond, T., Borsos, É., Barna, J., Erdélyi, P., Takács‐Vellai, K., Orosz, L., Kovács, A., Csikós, G., Sass, M., et al. (2008) · Autophagy · doi:10.4161/auto.5618 · Cited by 429 · see citing works
A dual role of p53 in the control of autophagy
Tasdemir, E., Maiuri, M. C., Morselli, E., Criollo, A., D’Amelio, M., Djavaheri‐Mergny, M., Cecconi, F., Tavernarakis, N., & Kroemer, G. (2008) · Autophagy · doi:10.4161/auto.6486 · Cited by 345 · see citing works
Self-citationAutophagy is Required for Dietary Restriction-Mediated Life Span Extension in<i>C. elegans</i>
Jia, K., & Levine, B. (2007) · Autophagy · doi:10.4161/auto.4989 · Cited by 341 · see citing works
Feng, Z., Hu, W., Teresky, A. K., Hernando, E., Cordon-Cardo, C., & Levine, A. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708043104 · Cited by 264 · see citing works
Autophagy Regulates Ageing in<i>C. elegans</i>
Hars, E. S., Qi, H., Jin, S. V., Cai, L., Hu, C., & Liu, L. F. (2007) · Autophagy · doi:10.4161/auto.3636 · Cited by 238 · see citing works
Autophagy is required for necrotic cell death in Caenorhabditis elegans
Samara, C., Syntichaki, P., & Tavernarakis, N. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402231 · Cited by 178 · see citing works
Self-citationPremature aging in mice activates a systemic metabolic response involving autophagy induction
Mariño, G., Ugalde, A. P., Salvador-Montoliu, N., Varela, I., Quirós, P. M., Cadiñanos, J., van der Pluijm, I., Freije, J. M. P., & López-Otı́n, C. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn120 · Cited by 143 · see citing works
Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice
Shiozaki, M., Yoshimura, K., Shibata, M., Koike, M., Matsuura∥, N., Uchiyama, Y., & Gotow, T. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.032 · Cited by 131 · see citing works
Cell Cycle-Dependent Induction of Autophagy, Mitophagy and Reticulophagy
Tasdemir, E., Maiuri, M. C., Tajeddine, N., Vitale, I., Criollo, A., Vicencio, J. M., Hickman, J. A., Geneste, O., & Kroemer, G. (2007) · Cell Cycle · doi:10.4161/cc.6.18.4681 · Cited by 123 · see citing works
Self-citationBauer, J. H., Poon, P. C., Glatt-Deeley, H. R., Abrams, J., & Helfand, S. L. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.051 · Cited by 121 · see citing works
Klionsky, D. J. (2004) · Nature · doi:10.1038/431031a · Cited by 82 · see citing works
Derry, W. B., Bierings, R., van Iersel, M., Satkunendran, T., Reinke, V., & Rothman, J. H. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402075 · Cited by 69 · see citing works
Caloric Restriction and Autophagy inCaenorhabditis elegans
Mörck, C., & Pilon, M. (2007) · Autophagy · doi:10.4161/auto.3418 · Cited by 29 · see citing works
Autophagy and Aging--When "All You Can Eat" Is Yourself
Cuervo, A. M. (2003) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2003.36.pe25 · Cited by 29 · see citing works
Flagged first, then by citations
Research works printed but not linked: 12
- Vicencio JM, Galluzzi L, Tajeddine N, Ortiz C, Criollo A, Tasdemir E, Morselli E, Ben Younes A, Maiuri MC, Lavandero S, Kroemer G. Senescence, apoptosis or autophagy? When a damaged cell must decide its path-a mini-review. Gerontology 2008; 54:92-9.
- Campisi J. Cancer and ageing: rival demons? Nat Rev Cancer 2003; 3:339-49.
- Donehower LA. p53: guardian AND suppressor of longevity? Exp Gerontol 2005; 40:7-9.
- Finkel T, Serrano M, Blasco MA. The common biology of cancer and ageing. Nature 2007; 448:767-74.
- Serrano M, Blasco MA. Cancer and ageing: convergent and divergent mechanisms. Nat Rev Mol Cell Biol 2007; 8:715-22.
- Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Hee Park S, Thompson T, Karsenty G, Bradley A, Donehower LA. p53 mutant mice that display early ageing-associated phenotypes. Nature 2002; 415:45-53.
- van Heemst D, Mooijaart SP, Beekman M, Schreuder J, de Craen AJ, Brandt BW, Slagboom PE, Westendorp RG; Long Life study group. Variation in the human TP53 gene affects old age survival and cancer mortality. Exp Gerontol 2005; 40:11-5.
- Orsted DD, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG. Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival and risk of cancer in the general population. J Exp Med 2007; 204:1295-301.
- Bojesen SE, Nordestgaard BG. The common germline Arg72Pro polymorphism of p53 and increased longevity in humans. Cell Cycle 2008; 7:158-63.
- Bauer JH, Chang C, Morris SN, Hozier S, Andersen S, Waitzman JS, Helfand SL. Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc Natl Acad Sci USA 2007; 104:13355-60.
- Arum O, Johnson TE. Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity. J Gerontol A Biol Sci Med Sci 2007; 62:951-9.
- Bergamini E, Cavallini G, Donati A, Gori Z. The role of autophagy in aging: its essential part in the anti-aging mechanism of caloric restriction. Ann NY Acad Sci 2007; 1114:69-78.
Cited by
Sorted by citations
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
Self-citationKlionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationRubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107 · see citing works
Self-citationInduction of autophagy by spermidine promotes longevity
Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1975 · Cited by 1,680 · see citing works
Cytoplasmic functions of the tumour suppressor p53
Green, D. R., & Kroemer, G. (2009) · Nature · doi:10.1038/nature07986 · Cited by 1,106 · see citing works
Self-citationAMP-Activated Protein Kinase (AMPK) Controls the Aging Process via an Integrated Signaling Network
Salminen, A., & Kaarniranta, K. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.12.005 · Cited by 860 · see citing works
Morselli, E., Maiuri, M. C., Markaki, M., Megalou, E., Pasparaki, A., Palikaras, K., Criollo, A., Galluzzi, L., Malik, S. A., Vitale, I., et al. (2010) · Cell Death & Disease · doi:10.1038/cddis.2009.8 · Cited by 613 · see citing works
Self-citationProtein Homeostasis and Aging: the importance of exquisite quality control
Koga, H., Kaushik, S., & Cuervo, A. M. (2011) · Ageing research reviews · doi:10.1016/j.arr.2010.02.001 · Cited by 476 · see citing works
Essential role for autophagy in life span extension
Madeo, F., Zimmermann, A., Maiuri, M. C., & Kroemer, G. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73946 · Cited by 464 · see citing works
Self-citationSpermidine induces autophagy by inhibiting the acetyltransferase EP300
Pietrocola, F., Lachkar, S., Enot, D. P., Niso-Santano, M., Bravo-San Pedro, J. M., Sica, V, Izzo, V, Maiuri, M. C., Madeo, F., Mariño, G., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.215 · Cited by 357 · see citing works
Self-citationThe Search for Antiaging Interventions: From Elixirs to Fasting Regimens
de Cabo, R., Carmona-Gutierrez, D., Bernier, M., Hall, M. N., & Madeo, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.031 · Cited by 345 · see citing works
Autophagy and the hallmarks of aging
Kaushik, S., Tasset, I., Arias, E., Pampliega, O., Wong, E., Martinez-Vicente, M., & Cuervo, A. M. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101468 · Cited by 285 · see citing works
Autophagy mediates pharmacological lifespan extension by spermidineand resveratrol
Morselli, E., Galluzzi, L., Kepp, O., Criollo, A., Maiuri, M. C., Tavernarakis, N., Madeo, F., & Kroemer, G. (2009) · Aging · doi:10.18632/aging.100110 · Cited by 213 · see citing works
Self-citationp53 ancestry: gazing through an evolutionary lens
Lu, W.-J., Amatruda, J. F., & Abrams, J. M. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2732 · Cited by 112 · see citing works
The Implications of Autophagy in Alzheimer’s Disease
Hamano, T., Hayashi, K., Shirafuji, N., & Nakamoto, Y. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666181004143432 · Cited by 57 · see citing works
- Authors
- Tavernarakis, N., Pasparaki, A., Tasdemir, E., Maiuri, M. C., & Kroemer, G.
- Affiliations
- FORTH Institute of Molecular Biology and Biotechnology (GR)
- Université Paris-Sud (FR)
- Inserm (FR)
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2008-08-18
- Volume
- 4
- Issue
- 7
- Pages
- 870-873
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W1994608257
- Cited by
- 132
- References
- 23
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 11 · 2015: 8 · 2014: 8 · 2013: 10 · 2012: 10
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ligue Contre le Cancer
- National Institutes of Health
- National Center for Research Resources
- 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
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- p53, biological aging, lifespan, CEP-1, Caenorhabditis elegans, RNA interference, tumor suppressor, longevity
- MeSH terms
- Animals, Autophagy, Longevity, Mutation, Tumor Suppressor Protein p53, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Vesicular Transport Proteins, RNA Interference
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