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Spermidine in health and disease
Abstract
Having your longevity and eating too: Although caloric restriction has clear benefits for maximizing health span and life span, it is sufficiently unpleasant that few humans stick to it. Madeo et al. review evidence that increased intake of the polyamine spermidine appears to reproduce many of the healthful effects of caloric restriction, and they explain its cellular actions, which include enhancement of autophagy and protein deacetylation. Spermidine is found in foods such as wheat germ, soybeans, nuts, and some fruits and vegetables and produced by the microbiota. Increased uptake of spermidine has protective effects against cancer, metabolic disease, heart disease, and neurodegeneration. Science , this issue p. eaan2788
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“Several CR-associated genes, including GPX3, HMGN2, NQO1 and ODC1 (encoding a rate-limiting enzyme of polyamine biosynthesis), possess or promote antioxidant activities61–66 (Fig. 5c–f and Supplementary Fig. 43a–d).”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [66]
In the citing paper
“Similarly, dietary supplementation with the polyamine spermidine prolongs life span and health span in several animal models66, and spermidine has also been shown to enhance memory performance and counteract age-related cognitive decline79–81.”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [66]
In the citing paper
“Polyamines are autophagy inducers33 that are implicated in immune regulation and have been shown to improve anti-cancer immunity in mice, synergizing with anti-PD ligand 1 immunotherapy22,34.”
From Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma (2024) · cites this paper as [33]
In the citing paper
“Thus, aging is linked to the decline of circulating spermidine and a-ketoglutarate, which are both endowed with anti-aging and anticancer properties.233,234”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [233]
In the citing paper
“Disabled autophagy due to progressive depletion of spermidine in aging tissues 233 can be expected to interfere with the immune recognition of cancer cells due the incapacity of dendritic cells to recognize autophagy-deficient cancer cells, as well as due to defective T lymphocyte and NK cell responses.163,252”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [233]
In the citing paper
“In particular, metabolites of the spermidine and kynurenine pathways are associated with the gut microbiota as well as the physiology of the host231,232.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [232]
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Metadata
- Authors
- Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G.
- Affiliations
- University of Graz (AT)
- Inserm (FR)
- Karolinska University Hospital (SE)
- Corresponding author
- Madeo, Frank
- Eisenberg, Tobias
- Kroemer, Guido
- Venue
- Science
- Published
- 2018-01-26
- Volume
- 359
- Issue
- 6374
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2784734859
- Cited by
- 1,154
- References
- 275
- Citations by year
- 2026: 179 · 2025: 179 · 2024: 154 · 2023: 132 · 2022: 150 · 2021: 113 · 2020: 122 · 2019: 74 · 2018: 50
- FWCI
- 6.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- European Commission (ERA-Net for Research on Rare Diseases)
- European Research Council
- Agence Nationale de la Recherche (Projets blancs)
- Fondation Leducq
- Austrian Science Fund (P23490-B20, P29262, P24381, P29203 P27893, I1000, W1226, and ‘SFB Lipotox’ (F3012))
- FFG Austria (COIN-project 855987)
- RHU Torino Lumière
- SIRIC Cancer Research and Personalized Medicine
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Labex
- Institut Universitaire de France
- Institut National Du Cancer
- Cancéropôle Île-de-France
- BMWFW Austria and the Karl-Franzens University
- 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 › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- spermidine, polyamines, caloric restriction mimetics, aging, age-related diseases, cardioprotection, neuroprotection, mitochondrial function, anti-inflammatory activity, stem cell senescence, protein deacetylation, autophagy, cardiovascular mortality, cancer mortality
- MeSH terms
- Aging, Animals, Anti-Inflammatory Agents, Non-Steroidal, Autophagy, Biological Transport, Cardiovascular Diseases, Humans, Spermidine, Neuroprotective Agents, Dietary Supplements, Metabolic Syndrome, Caloric Restriction, Carcinogenesis
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