Spermidine: A physiological autophagy inducer acting as an anti-aging vitamin in humans?
Open accessAbstract
Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested. Recent epidemiological data support this notion, showing that an increased uptake of this polyamine with spermidine-rich food diminishes overall mortality associated with cardiovascular diseases and cancer. Here, we discuss nutritional and other possible routes to counteract the age-mediated decline of spermidine levels.
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Spermidine is an effective antiaging agent.
“and has been shown to be an effective antiaging agent [275,276,277].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [277]
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Cites
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 · see citing works
Autophagy in Human Health and Disease
Choi, A. M. K., Ryter, S. W., & Levine, B. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1205406 · Cited by 2,583 · see citing works
Rubinsztein, 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
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 · see citing works
Self-citationSpermidine in health and disease
Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018) · Science · doi:10.1126/science.aan2788 · Cited by 1,154 · see citing works
Self-citationModulation of cellular function by polyamines
Igarashi, K., & Kashiwagi, K. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.07.009 · Cited by 852 · see citing works
Mammalian polyamine metabolism and function
Pegg, A. E. (2009) · IUBMB Life · doi:10.1002/iub.230 · Cited by 786 · see citing works
Functions of Polyamines in Mammals
Pegg, A. E. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.731661 · Cited by 720 · see citing works
Autophagy: machinery and regulation
Yin, Z., Pascual, C., & Klionsky, D. J. (2016) · Microbial Cell · doi:10.15698/mic2016.12.546 · Cited by 567 · see citing works
Caloric restriction mimetics enhance anticancer immunosurveillance
Pietrocola, F., Pol, J., Vacchelli, E., Rao, S., Enot, D. P., Baracco, E. E., Levesque, S., Castoldi, F., Jacquelot, N., Yamazaki, T., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.05.016 · Cited by 542 · see citing works
Zhang, C., & Cuervo, A. M. (2008) · Nature Medicine · doi:10.1038/nm.1851 · Cited by 520 · see citing works
Regulation of autophagy by cytosolic acetyl-coenzyme A
Mariño, G., Pietrocola, F., Eisenberg, T., Kong, Y., Malik, S. A., Andryushkova, A., Schroeder, S., Pendl, T., Harger, A., Niso-Santano, M., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.01.016 · Cited by 500 · see citing works
Wang, I.-F., Guo, B.-S., Liu, Y.-C., Wu, C.-C., Yang, C.-H., Tsai, K.-J., & Shen, C.-K. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206362109 · Cited by 377 · see citing works
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner
Gupta, V., Scheunemann, L., Eisenberg, T., Mertel, S., Bhukel, A., Koemans, T. S., Kramer, J. M., Liu, K. S. Y., Schroeder, S., Stunnenberg, H. G., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3512 · Cited by 374 · see citing works
Self-citationRapamycin extends murine lifespan but has limited effects on aging
Neff, F., Flores-Dominguez, D., Ryan, D. P., Horsch, M., Schröder, S., Adler, T., Afonso, L. C., Aguilar-Pimentel, J. A., Becker, L., Garrett, L., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67674 · Cited by 374 · see citing works
Autophagy is a critical regulator of memory CD8+ T cell formation
Puleston, D. J., Zhang, H., Powell, T. J., Lipina, E., Sims, S., Panse, I., Watson, A. S., Cerundolo, V., Townsend, A. R., Klenerman, P., et al. (2014) · eLife · doi:10.7554/elife.03706 · Cited by 360 · see citing works
Spermidine 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-citationImpact of intestinal microbiota on intestinal luminal metabolome
Matsumoto, M., Kibe, R., Ooga, T., Aiba, Y., Kurihara, S., Sawaki, E., Koga, Y., & Benno, Y. (2012) · Scientific Reports · doi:10.1038/srep00233 · Cited by 334 · see citing works
Autophagy and neurodegeneration
Frake, R. A., Ricketts, T., Menzies, F. M., & Rubinsztein, D. C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73944 · Cited by 332 · see citing works
Polyamines and cancer: implications for chemotherapy and chemoprevention
Nowotarski, S. L., Woster, P. M., & Casero, R. A. (2013) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2013.3 · Cited by 304 · see citing works
Matsumoto, M., Kurihara, S., Kibe, R., Ashida, H., & Benno, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023652 · Cited by 290 · cited 1× · see citing works
“Therefore, blood levels of spermidine and spermine can be upregulated through oral administration of the polyamine-producing probiotic Bifidobacterium LKM512, resulting in suppressed inflammation and improved longevity in old mice [35].”
BackgroundKibe, R., Kurihara, S., Sakai, Y., Suzuki, H., Ooga, T., Sawaki, E., Muramatsu, K., Nakamura, A., Yamashita, A., Kitada, Y., et al. (2014) · Scientific Reports · doi:10.1038/srep04548 · Cited by 271 · see citing works
The importance of dietary polyamines in cell regeneration and growth
Bardócz, S., Duguid, T. J., Brown, D. S., Grant, G., Pusztai, A. J., White, A. L., & Ralph, A. (1995) · British Journal Of Nutrition · doi:10.1079/bjn19950087 · Cited by 269 · see citing works
Higher spermidine intake is linked to lower mortality: a prospective population-based study
Kiechl, S. J., Pechlaner, R., Willeit, P., Notdurfter, M., Paulweber, B., Willeit, K., Werner, P., Ruckenstuhl, C., Iglseder, B., Weger, S., et al. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy102 · Cited by 251 · see citing works
Self-citationThe crucial impact of lysosomes in aging and longevity
Carmona‐Gutiérrez, D., Hughes, A. L., Madeo, F., & Ruckenstuhl, C. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.009 · Cited by 244 · see citing works
Self-citationThe mitochondrial pathway in yeast apoptosis
Eisenberg, T., Büttner, S., Kroemer, G., & Madeo, F. (2007) · APOPTOSIS · doi:10.1007/s10495-007-0758-0 · Cited by 229 · see citing works
Self-citationHistone deacetylase 10 structure and molecular function as a polyamine deacetylase
Hai, Y., Shinsky, S. A., Porter, N. J., & Christianson, D. W. (2017) · Nature Communications · doi:10.1038/ncomms15368 · Cited by 200 · see citing works
Yue, F., Li, W., Zou, J., Jiang, X., Xu, G., Huang, H. W., & Liu, L. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-3462 · Cited by 176 · see citing works
Schwarz, C., Stekovic, S., Wirth, M., Benson, G. S., Royer, P., Sigrist, S. J., Pieber, T. R., Dammbrueck, C., Magnes, C., Eisenberg, T., et al. (2018) · Aging · doi:10.18632/aging.101354 · Cited by 165 · see citing works
Self-citationYang, Q., Zheng, C., Cao, J., Cao, G., Shou, P., Lin, L., Velletri, T., Jiang, M., Chen, Q., Han, Y., et al. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.71 · Cited by 161 · see citing works
Polyamines in the gut lumen: bioavailability and biodistribution
Milović, V. (2001) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200109000-00004 · Cited by 159 · see citing works
Long-Term Oral Polyamine Intake Increases Blood Polyamine Concentrations
Soda, K., Kano, Y., SAKURAGI, M., Takao, K., Lefor, A. K., & Konishi, F. (2009) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.55.361 · Cited by 153 · see citing works
Spermidine and spermine are enriched in whole blood of nona/centenarians
Pucciarelli, S., Moreschini, B., Micozzi, D., De Fronzo, G. S., Carpi, F. M., Polzonetti, V., Vincenzetti, S., Mignini, F., & Napolioni, V. (2012) · Rejuvenation Research · doi:10.1089/rej.2012.1349 · Cited by 144 · see citing works
Jell, J., Merali, S., Hensen, M. L., Mazurchuk, R. V., Spernyak, J. A., Diegelman, P., Kisiel, N. D., Barrero, C. A., Deeb, K. K., Alhonen, L. I., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m610265200 · Cited by 138 · see citing works
Matsumoto, M., & Benno, Y. (2007) · Microbiology and Immunology · doi:10.1111/j.1348-0421.2007.tb03887.x · Cited by 129 · see citing works
Metabolic effects of fasting on human and mouse blood in vivo
Pietrocola, F., Demont, Y., Castoldi, F., Enot, D. P., Durand, S., Semeraro, M., Baracco, E. E., Pol, J. G., Pedro, J. M. B., Bordenave, C., et al. (2017) · Autophagy · doi:10.1080/15548627.2016.1271513 · Cited by 106 · see citing works
Self-citationKee, K., Foster, B. A., Merali, S., Kramer, D. L., Hensen, M. L., Diegelman, P., Kisiel, N. D., Vujcic, S., Mazurchuk, R. V., & Porter, C. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406002200 · Cited by 94 · see citing works
Polyamines in mammalian ageing: An oncological problem, too? A review
Scalabrino, G., & Ferioli, M. E. (1984) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(84)90090-3 · Cited by 91 · see citing works
New roles for autophagy and spermidine in T cells
Puleston, D. J., & Simon, A. K. (2015) · Microbial Cell · doi:10.15698/mic2015.03.195 · Cited by 19 · see citing works
The Precision Control of Autophagic Flux and Vesicle Dynamics—A Micropattern Approach
du Toit, A., de Wet, S., Hofmeyr, J. S., Müller-Nedebock, K. K., & Loos, B. (2018) · Cells · doi:10.3390/cells7080094 · Cited by 16 · see citing works
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Fries, G. R., Saldana, V. A., Finnstein, J., & Rein, T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01806-1 · Cited by 504 · see citing works
Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia
Connell, E., Le Gall, G., Pontifex, M. G., Sami, S., Cryan, J. F., Clarke, G., Müller, M., & Vauzour, D. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00548-6 · Cited by 208 · see citing works
Targeting aging mechanisms: pharmacological perspectives
Moskalev, A., Guvatova, Z., Lopes, I. D. A., Beckett, C. W., Kennedy, B. K., De Magalhaes, J. P., & Makarov, A. A. (2022) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2022.01.007 · Cited by 164 · see citing works
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Rottenberg, H., & Hoek, J. B. (2021) · Cells · doi:10.3390/cells10010079 · Cited by 94 · see citing works
Yang, Y., & Zhang, L. (2020) · Food & Function · doi:10.1039/c9fo02611h · Cited by 57 · see citing works
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Self-citation
- Authors
- Madeo, F., Bauer, M. A., Carmona-Gutierrez, D., & Kroemer, G.
- Affiliations
- University of Graz (AT)
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
- Karolinska University Hospital (SE)
- Corresponding author
- Madeo, Frank
- Kroemer, Guido
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2018-10-11
- Volume
- 15
- Issue
- 1
- Pages
- 165-168
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC6287690
- OpenAlex
- W2896631314
- Cited by
- 212
- References
- 41
- Citations by year
- 2026: 33 · 2025: 35 · 2024: 31 · 2023: 28 · 2022: 27 · 2021: 23 · 2020: 27 · 2019: 8
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Autophagy (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- Agence Nationale de la Recherche (E-Rare-2, Projets blancs)
- Austrian Science Fund (W1226, P29262)
- Austrian Science Fund (AT) (F3012, I1000, P29203, P24381, P23490-B20, P27893)
- Bundesministerium für Wissenschaft, Forschung und Wirtschaft (AT) (Unkonventionelle Forschung)
- BioTechMed-Graz/NAWI Graz (EPIAge)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- spermidine, polyamines, macroautophagy, anti-aging, lifespan extension, healthspan, aging, dietary supplementation, mortality, cardiovascular disease, cancer, age-related decline
- MeSH terms
- Aging, Animals, Autophagy, Humans, Nematoda, Spermidine, Vitamins, Yeasts, Up-Regulation, Mice
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