Spermidine in health and disease

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Spermidine suppresses oxidative stress and ferroptosis by Nrf2/HO-1/GPX4 and Akt/FHC/ACSL4 pathway to alleviate ovarian damage

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Nutrition and longevity—From mechanisms to uncertainties

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Assessing the role of amino acids in systemic inflammation and organ failure in patients with ACLF

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Immunoregulatory Interplay Between Arginine and Tryptophan Metabolism in Health and Disease

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Polyamines and Their Metabolism: From the Maintenance of Physiological Homeostasis to the Mediation of Disease

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Spermidine Ameliorates Colitis via Induction of Anti-Inflammatory Macrophages and Prevention of Intestinal Dysbiosis

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Spermidine inhibits neurodegeneration and delays aging via the PINK1-PDR1-dependent mitophagy pathway in C. elegans

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Untargeted metabolomics yields insight into ALS disease mechanisms

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Cancer pharmacoprevention: Targeting polyamine metabolism to manage risk factors for colon cancer

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Recent advances in the field of caloric restriction mimetics and anti-aging molecules

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Are mitophagy enhancers therapeutic targets for Alzheimer’s disease?

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Spermidine rescues the deregulated autophagic response to oxidative stress of osteoarthritic chondrocytes

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Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells

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Spermidine‐Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ

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Spermidine Confers Liver Protection by Enhancing NRF2 Signaling Through a MAP1S‐Mediated Noncanonical Mechanism

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Femtomolar Detection of Spermidine Using Au Decorated SiO2 Nanohybrid on Plasmon-Coupled Extended Cavity Nanointerface: A Smartphone-Based Fluorescence Dequenching Approach

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Polyamines in mammalian pathophysiology

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Antiaging effects of bioactive molecules isolated from plants and fungi

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Space Radiation Protection Countermeasures in Microgravity and Planetary Exploration

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Gut-microbiota derived bioactive metabolites and their functions in host physiology

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The Effects and Mechanisms of Flavonoids on Cancer Prevention and Therapy: Focus on Gut Microbiota

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Polyamine metabolism controls B-to-Z DNA transition to orchestrate DNA sensor cGAS activity

Zhao, C., Ma, Y., Zhang, M., Gao, X., Liang, W., Qin, Y., Fu, Y., Jia, M., Song, H., Gao, C., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.09.012 · Cited by 83

Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia

Gong, S., Sovio, U., Aye, I. L. M. H., Gaccioli, F., Dopierala, J., Johnson, M. D., Wood, A., Cook, E., Jenkins, B., Koulman, A., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120723 · Cited by 79

Role of mitophagy in mitochondrial quality control: Mechanisms and potential implications for neurodegenerative diseases

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Effect of Methionine Restriction on Aging: Its Relationship to Oxidative Stress

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Mitochondrial immune regulation and anti-tumor immunotherapy strategies targeting mitochondria

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Regulation of Cell Death Induced by Acetic Acid in Yeasts

Chaves, S. R., Rego, A., Martins, V. M., Santos‐Pereira, C., Sousa, M. J., & Côrte‐Real, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.642375 · Cited by 75

Digesting the crisis: autophagy and coronaviruses

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Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders

Ghosh, I., Sankhe, R., Mudgal, J., Arora, D. S., & Nampoothiri, M. (2020) · Neuropeptides · doi:10.1016/j.npep.2020.102083 · Cited by 74

The role of polyamine metabolism in remodeling immune responses and blocking therapy within the tumor immune microenvironment

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Autophagy within the mushroom body protects from synapse aging in a non-cell autonomous manner

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Spermidine as a target for cancer therapy

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Host and microbiota metabolic signals in aging and longevity

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Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity

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Calorie Restriction Mimetics: Upstream-Type Compounds for Modulating Glucose Metabolism

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Maintaining the balance of TDP-43, mitochondria, and autophagy: a promising therapeutic strategy for neurodegenerative diseases

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Sequential multi-omics analysis identifies clinical phenotypes and predictive biomarkers for long COVID

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Advancements in therapeutic drugs targeting of senescence

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Spermidine Suppresses Inflammatory DC Function by Activating the FOXO3 Pathway and Counteracts Autoimmunity

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Dietary strategies with anti-aging potential: Dietary patterns and supplements

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Spermidine ameliorates non-alcoholic fatty liver disease through regulating lipid metabolism via AMPK

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Increasing Polyamine Contents Enhances the Stress Tolerance via Reinforcement of Antioxidative Properties

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Pharmacological polyamine catabolism upregulation with methionine salvage pathway inhibition as an effective prostate cancer therapy

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Calorie Restriction for Cancer Prevention and Therapy: Mechanisms, Expectations, and Efficacy

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Dietary Mitophagy Enhancer: A Strategy for Healthy Brain Aging?

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Nutrients and Pathways that Regulate Health Span and Life Span

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Spermidine – an old molecule with a new age-defying immune function

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Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial

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Impaired eIF5A function causes a Mendelian disorder that is partially rescued in model systems by spermidine

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Polyamine Homeostasis in Development and Disease

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Therapeutic modulation of autophagy: which disease comes first?

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FTIR and PLS-regression in the evaluation of bioactive amines, total phenolic compounds and antioxidant potential of dark chocolates

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Engineering yeast metabolism for the discovery and production of polyamines and polyamine analogues

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Meta-analysis of shotgun sequencing of gut microbiota in Parkinson’s disease

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Microbial diversity and chemical analysis of Shuidouchi, traditional Chinese fermented soybean

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The metabolomic signature of extreme longevity: naked mole rats versus mice

Viltard, M., Durand, S., Pérez-Lanzón, M., Aprahamian, F., Lefevre, D., Leroy, C., Madeo, F., Kroemer, G., & Friedlander, G. (2019) · Aging · doi:10.18632/aging.102116 · Cited by 63

Serine and Metabolism Regulation: A Novel Mechanism in Antitumor Immunity and Senescence

Wu, Q., Chen, X., Li, J., & Sun, S. (2020) · Aging and Disease · doi:10.14336/ad.2020.0314 · Cited by 65

Gut microbiome and metabolites, the future direction of diagnosis and treatment of atherosclerosis?

Cao, H., Zhu, Y., Hu, G., Zhang, Q., & Zheng, L. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106586 · Cited by 64

Tumor Microenvironment Mediated Spermidine-Metal-Immunopeptide Nanocomplex for Boosting Ferroptotic Immunotherapy of Lymphoma

Nie, T., Liu, H., Fang, Z., Zheng, Y., Zhang, R., Xu, X., Liu, S., & Wu, J. (2023) · ACS Nano · doi:10.1021/acsnano.3c02803 · Cited by 62

Gut microbiota and anti-aging: Focusing on spermidine

Yu, L., Pan, J., Guo, M., Duan, H., Zhang, H., Narbad, A., Zhai, Q., Tian, F., & Chen, W. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2224867 · Cited by 63

Role of eIF5A in Mitochondrial Function

Barba‐Aliaga, M., & Alepuz, P. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031284 · Cited by 63

Phenolamide and flavonoid glycoside profiles of 20 types of monofloral bee pollen

Qiao, J., Feng, Z., Zhang, Y., Xiao, X., Dong, J. N., Haubruge, É., & Zhang, H. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.134800 · Cited by 60

Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator

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Tetracyclines promote survival and fitness in mitochondrial disease models

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Spermidine ameliorates high-fat diet-induced hepatic steatosis and adipose tissue inflammation in preexisting obese mice

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Spermine Induces Autophagy in Plants: Possible Role of NO and Reactive Oxygen Species

Анатольевна, Д. С., Ponomareva, A. A., Gurjanov, O. P., Mazina, A. B., Андрианов, В. В., Iyudin, V. S., & Minibayeva, F. V. (2018) · Doklady Biochemistry and Biophysics · doi:10.1134/s1607672918060121 · Cited by 58

The Polyamine Spermidine Modulates the Production of the Bacterial Genotoxin Colibactin

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Metabolic characterization of hypertrophic cardiomyopathy in human heart

Wang, W., Wang, J., Yao, K., Wang, S., Nie, M., Zhao, Y., Wang, B., Pang, H., Xu, J., Wu, G., et al. (2022) · Nature Cardiovascular Research · doi:10.1038/s44161-022-00057-1 · Cited by 58

Tumor cell–derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8 + T cell activation

Hibino, S., Eto, S., Hangai, S., Endo, K., Ashitani, S., Sugaya, M., Osawa, T., Soga, T., Taniguchi, T., & Yanai, H. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2305245120 · Cited by 58

Molecular mechanisms of mitophagy and its roles in neurodegenerative diseases

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Lactobacillus plantarum prevents obesity via modulation of gut microbiota and metabolites in high-fat feeding mice

Li, X., Huang, Y., Song, L., Xiao, Y., Lu, S., Xu, J., Li, J., & Ren, Z. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.104103 · Cited by 57

Occurrence of Polyamines in Foods and the Influence of Cooking Processes

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Effect of Hesperidin Supplementation on Liver Metabolomics and Gut Microbiota in a High-Fat Diet-Induced NAFLD Mice Model

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Assessment of the safety and probiotic properties of Roseburia intestinalis: A potential “Next Generation Probiotic”

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Autophagy in sarcopenia: Possible mechanisms and novel therapies

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Alzheimer’s disease as a chronic maladaptive polyamine stress response

Polis, B., Karasik, D., & Samson, A. O. (2021) · Aging · doi:10.18632/aging.202928 · Cited by 62

The positive effect of spermidine in older adults suffering from dementia: First results of a 3-month trial

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Multi-omics Analysis Revealed Coordinated Responses of Rumen Microbiome and Epithelium to High-Grain-Induced Subacute Rumen Acidosis in Lactating Dairy Cows

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Sulfide regulation and catabolism in health and disease

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Distinct Immunomodulatory Effects of Spermine Oxidase in Colitis Induced by Epithelial Injury or Infection

Gobert, A. P., Al-Greene, N. T., Singh, K., Coburn, L. A., Sierra, J. C., Verriere, T. G., Luis, P. B., Schneider, C. G., Asim, M., Allaman, M. M., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01242 · Cited by 56

Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation

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Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses

Maglione, M., Kochlamazashvili, G., Eisenberg, T., Rácz, B., Michael, E., Toppe, D., Stumpf, A., Wirth, A., Zeug, A., Müller, F. E., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-56133-3 · Cited by 58

Use of the Versatility of Fungal Metabolism to Meet Modern Demands for Healthy Aging, Functional Foods, and Sustainability

Takahashi, J., Barbosa, B., Martins, B. D. A., Guirlanda, C. P., & Moura, M. (2020) · Journal of Fungi · doi:10.3390/jof6040223 · Cited by 40

Metabolic regulation in the immune response to cancer

Wu, Q., Yu, X., Li, J., Sun, S., & Tu, Y. (2021) · 癌症：英文版 · doi:10.1002/cac2.12182 · Cited by 57

Epigallocatechin Gallate Effectively Affects Senescence and Anti-SASP via SIRT3 in 3T3-L1 Preadipocytes in Comparison with Other Bioactive Substances

Lilja, S., Oldenburg, J., Pointner, A., Dewald, L., Lerch, M. L., Hippe, B., Switzeny, O. J., & Haslberger, A. G. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/4793125 · Cited by 58

Bioaccessibility of phenolic acids in Canadian hulless barley varieties

Drawbridge, P. C., Apea-Bah, F. B., Hornung, P. S., & Trust Beta (2021) · Food Chemistry · doi:10.1016/j.foodchem.2021.129905 · Cited by 53

Recent updates on the role of the gut-liver axis in the pathogenesis of NAFLD/NASH, HCC, and beyond

Ohtani, N., Kamiya, T., & Kawada, N. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000241 · Cited by 55

α-Ketoglutarate inhibits autophagy

Baracco, E. E., Castoldi, F., Durand, S., Enot, D. P., Tadić, J., Kainz, K., Madeo, F., Chery, A., Izzo, V., Maiuri, M. C., et al. (2019) · Aging · doi:10.18632/aging.102001 · Cited by 55

Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and d-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging

Singh, S., Kumar, R., Garg, G., Singh, A. K., Verma, A. K., Bissoyi, A., & Rizvi, S. I. (2020) · Biogerontology · doi:10.1007/s10522-020-09900-z · Cited by 54

Spermidine intake is associated with cortical thickness and hippocampal volume in older adults

Schwarz, C., Horn, N., Benson, G. S., Calzado, I. W., Wurdack, K., Pechlaner, R., Grittner, U., Wirth, M., & Flöel, A. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.117132 · Cited by 54

Molecular mechanisms and clinical implications of multiple forms of mitophagy in the heart

Saito, T., Hamano, K., & Sadoshima, J. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa340 · Cited by 50

Peroxiredoxin 3 deficiency induces cardiac hypertrophy and dysfunction by impaired mitochondrial quality control

Sonn, S. K., Song, E. J., Seo, S., Kim, Y. Y., Um, J., Yeo, F. J., Lee, D. S., Jeon, S., Lee, M.-N., Jin, J., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102275 · Cited by 53

Long-distance microbial mechanisms impacting cancer immunosurveillance

Zitvogel, L., Fidelle, M., & Kroemer, G. (2024) · Immunity · doi:10.1016/j.immuni.2024.07.020 · Cited by 56

Lysosomal dysfunction in α-synuclein pathology: molecular mechanisms and therapeutic strategies

Dai, L., Liu, M., Ke, W., Chen, L., Fang, X., & Zhang, Z. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05419-5 · Cited by 53

Spermidine/spermine N1-acetyltransferase-mediated polyamine catabolism regulates beige adipocyte biogenesis

Yuan, F., Zhang, L., Cao, Y., Gao, W. Q., Zhao, C., Fang, Y., Zahedi, K. A., Soleimani, M., Lü, X., Fang, Z., et al. (2018) · Metabolism · doi:10.1016/j.metabol.2018.04.007 · Cited by 51

Type 2 Diabetes Is Associated with a Different Pattern of Serum Polyamines: A Case–Control Study from the PREDIMED-Plus Trial

Fernández‐García, J. C., Delpino-Rius, A., Samarra, I., Castellano‐Castillo, D., Muñoz‐Garach, A., Bernal-López, M. R., Queipo‐Ortuño, M. I., Cardona, F., Ramos‐Molina, B., & Tinahones, F. J. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8010071 · Cited by 51

Nutraceuticals Targeting Generation and Oxidant Activity of Peroxynitrite May Aid Prevention and Control of Parkinson’s Disease

McCarty, M. F., & Lerner, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103624 · Cited by 51

Convergence of Plasma Metabolomics and Proteomics Analysis to Discover Signatures of High-Grade Serous Ovarian Cancer

Ahn, H., Yeom, J., Yu, J., Kwon, Y.-I., Kim, J., & Kim, K. (2020) · Cancers · doi:10.3390/cancers12113447 · Cited by 51

Citrulline regulates macrophage metabolism and inflammation to counter aging in mice

Xie, Z., Lin, M., Xing, B., Wang, H., Zhang, H., Cai, Z., Mei, X., & Zhu, Z. (2025) · Science Advances · doi:10.1126/sciadv.ads4957 · Cited by 51

Mechanisms of spermidine-induced autophagy and geroprotection

Hofer, S. J., Simon, A. K., Bergmann, M., Eisenberg, T., Kroemer, G., & Madeo, F. (2022) · Nature Aging · doi:10.1038/s43587-022-00322-9 · Cited by 218

Geroprotective insights into the natural metabolite spermidine in aging and age-related diseases

Jiang, Z., Tong, S., Kirkland, J. L., & Sun, Y. (2026) · npj Aging · doi:10.1038/s41514-026-00448-9

Molecular targets of spermidine: implications for cancer suppression

Zimmermann, A., Hofer, S. J., & Madeo, F. (2023) · Cell Stress · doi:10.15698/cst2023.07.281 · Cited by 23

Cardioprotective benefits of dietary spermidine

Huynh, K. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.222 · Cited by 4

Spermidine: A physiological autophagy inducer acting as an anti-aging vitamin in humans?

Madeo, F., Bauer, M. A., Carmona-Gutierrez, D., & Kroemer, G. (2019) · Autophagy · doi:10.1080/15548627.2018.1530929 · Cited by 212