Spermidine in health and disease

The Hallmarks of Aging

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Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases

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Inflamm‐aging: An Evolutionary Perspective on Immunosenescence

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Immunogenic cell death in cancer and infectious disease

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Extending Healthy Life Span—From Yeast to Humans

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Autophagy and Aging

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FoxO3 Controls Autophagy in Skeletal Muscle In Vivo

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Targeting mitochondrial fitness as a strategy for healthy vascular aging

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Compromised autophagy and mitophagy in brain ageing and Alzheimer’s diseases.

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Exogenous spermine attenuates myocardial fibrosis in diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress and the canonical Wnt signaling pathway

Hu, J. R., Lu, X., Zhang, X., Shao, X., Wang, Y., Chen, J., Zhao, B., Li, S., Xu, C., & Wei, C. (2020) · Cell Biology International · doi:10.1002/cbin.11360 · Cited by 49

High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study

Senekowitsch, S., Wietkamp, E., Grimm, M. F., Schmelter, F., Schick, P., Kordowski, A., Sina, C., Otzen, H., Weitschies, W., & Smollich, M. (2023) · Nutrients · doi:10.3390/nu15081852 · Cited by 50

Gut microbiome and bone health: update on mechanisms, clinical correlations, and possible treatment strategies

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Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats

Aldea, M., Olaru, A., Udriștoiu, I., Mărgăritescu, C., Petcu, E. B., Hermann, D. M., & Popa‐Wagner, A. (2020) · GeroScience · doi:10.1007/s11357-020-00173-5 · Cited by 49

Spermidine induces cytoprotective autophagy of female germline stem cells in vitro and ameliorates aging caused by oxidative stress through upregulated sequestosome-1/p62 expression

Yuan, X., Tian, G. G., Pei, X., Hu, X., & Wu, J. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00614-4 · Cited by 48

Aging-associated accumulation of mitochondrial DNA mutations in tumor origin

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Lactobacillus reuteri ZJ617 attenuates metabolic syndrome via microbiota-derived spermidine

Ma, Y., Zhong, Y., Tang, W., Valencak, T. G., Liu, J., Deng, Z., Mao, J., Liu, D., Wang, S., Wang, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56105-4 · Cited by 50

Neuronal Mitophagy: Friend or Foe?

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New Insights Into Permeation of Large Cations Through ATP-Gated P2X Receptors

Peverini, L., Beudez, J., Dunning, K., Chataigneau, T., & Grütter, T. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00265 · Cited by 47

Spermidine reduces cancer-related mortality in humans

Pietrocola, F., Castoldi, F., Kepp, O., Carmona‐Gutiérrez, D., Madeo, F., & Kroemer, G. (2018) · Autophagy · doi:10.1080/15548627.2018.1539592 · Cited by 46

Targeting Myocardial Mitochondria-STING-Polyamine Axis Prevents Cardiac Hypertrophy in Chronic Kidney Disease

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Amino Acid Metabolism and Atherosclerotic Cardiovascular Disease

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Autophagy in Metabolic Age-Related Human Diseases

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Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2

Tillinghast, J., Drury, S., Bowser, D., Benn, A., & Lee, K. P. K. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.10.002 · Cited by 45

SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer

Ding, Y., Feng, Y., Huang, Z., Zhang, Y., Li, X., Liu, R., Li, H., Wang, T., Ding, Y., Jia, Z., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05108-w · Cited by 45

T cell aging as a risk factor for autoimmunity

Liu, Q., Zheng, Y., Goronzy, J. J., & Weyand, C. M. (2022) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102947 · Cited by 48

Role of polyamines in intestinal mucosal barrier function

Nakamura, A., & Matsumoto, M. (2025) · Seminars in Immunopathology · doi:10.1007/s00281-024-01035-4 · Cited by 46

Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer’s Disease: A Systematic Review

Gruendler, R., Hippe, B., Jengić, V. Š., Peterlin, B., & Haslberger, A. G. (2020) · Molecules · doi:10.3390/molecules25246018 · Cited by 47

Spermidine protects against acute kidney injury by modulating macrophage NLRP3 inflammasome activation and mitochondrial respiration in an eIF5A hypusination-related pathway

Li, X., Zhou, X., Liu, X., Li, X., Jiang, X., Shi, B., & Wang, S. (2022) · Molecular Medicine · doi:10.1186/s10020-022-00533-1 · Cited by 45

The microbiome in spondyloarthritis

Bréban, M., Beaufrère, M., & Glatigny, S. (2019) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2020.101495 · Cited by 44

A viscoelastic alginate-based hydrogel network coordinated with spermidine for periodontal ligament regeneration

Zhang, S., Jia, Y., Liu, J., Feng, F., Zhao, W., Zhang, M., & Xu, F. (2023) · Regenerative Biomaterials · doi:10.1093/rb/rbad009 · Cited by 43

Spermidine as an epigenetic regulator of autophagy in neurodegenerative disorders

Satarker, S., Wilson, J., Kolathur, K. K., Mudgal, J., Lewis, S. A., Arora, D. S., & Nampoothiri, M. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176823 · Cited by 43

Intracellular second messengers mediate stress inducible hormesis and Programmed Cell Death: A review

Zhou, D. R., Eid, R., Miller, K. A., Boucher, É. L., Mandato, C. A., & Greenwood, M. T. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.01.016 · Cited by 43

Spermidine Prevents Heart Injury in Neonatal Rats Exposed to Intrauterine Hypoxia by Inhibiting Oxidative Stress and Mitochondrial Fragmentation

Chai, N., Zhang, H., Li, L., Yu, X. M., Liu, Y., Yan, L., Wang, L., Yan, J., Николаевна, С. Е., & Zhao, Y. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/5406468 · Cited by 45

Hypusination Orchestrates the Antimicrobial Response of Macrophages

Gobert, A. P., Finley, J. L., Latour, Y. L., Asim, M., Smith, T. M., Verriere, T. G., Barry, D. P., Allaman, M. M., Delagado, A. G., Rose, K. L., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108510 · Cited by 44

Understanding amino acids and bioactive amines changes during on-farm cocoa fermentation

Deus, V. L., Bispo, E. S., França, A. S., & Glória, M. B. A. (2020) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2020.103776 · Cited by 42

Free spermidine evokes superoxide radicals that manifest toxicity

Kumar, V., Mishra, R. K., Ghose, D., Kalita, A., Dhiman, P., Prakash, A., Thakur, N., Mitra, G., Chaudhari, V. D., Arora, A., et al. (2022) · eLife · doi:10.7554/elife.77704 · Cited by 42

Antiaging Mechanism of Natural Compounds: Effects on Autophagy and Oxidative Stress

Taylor, E., Kim, Y., Zhang, K., Chau, L., Nguyen, B. C., Rayalam, S., & Wang, X. (2022) · Molecules · doi:10.3390/molecules27144396 · Cited by 46

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

Machado, I. F., Palmeira, C. M., & Rolo, A. P. (2023) · Biomedicines · doi:10.3390/biomedicines11030948 · Cited by 41

Spermidine protects intestinal mucosal barrier function in mice colitis via the AhR/Nrf2 and AhR/STAT3 signaling pathways

Yan, B., Mao, X., Hu, S., Wang, S., Liu, X., & Sun, J. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110166 · Cited by 45

The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer’s disease

Jung, Y. H., Chae, C. W., & Han, H. J. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01282-3 · Cited by 47

Polyamine Deacetylase Structure and Catalysis: Prokaryotic Acetylpolyamine Amidohydrolase and Eukaryotic HDAC10

Shinsky, S. A., & Christianson, D. W. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00079 · Cited by 41

Serum polyamine metabolic profile in autoimmune thyroid disease patients

Song, J., Shan, Z., Mao, J., & Teng, W. (2019) · Clinical Endocrinology · doi:10.1111/cen.13946 · Cited by 43

Discovery of Gut Bacteria Specific to Alzheimer’s Associated Diseases is a Clue to Understanding Disease Etiology: Meta-Analysis of Population-Based Data on Human Gut Metagenomics and Metabolomics

Paley, E. L. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190873 · Cited by 41

The Autophagy–RNA Interplay: Degradation and Beyond

Abildgaard, M. H., Brynjólfsdóttir, S. H., & Frankel, L. B. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.07.007 · Cited by 42

The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies

Tse, R. T., Wong, C. Y., Chiu, P. K., & Ng, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031258 · Cited by 42

Effect of spermidine on ameliorating spermatogenic disorders in diabetic mice via regulating glycolysis pathway

Wang, J., Ma, D., Luo, M., Tan, Y.-P., Zhong, O., Tian, G., Lv, Y.-T., Li, M., Chen, X., Tang, Z., et al. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-00890-w · Cited by 41

Spermine enhances antiviral and anticancer responses by stabilizing DNA binding with the DNA sensor cGAS

Wang, L., Li, S., Wang, K., Wang, N., Liu, Q., Sun, Z., Wang, L., Wang, L., Liu, Q., Song, C., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.001 · Cited by 42

The hunger strikes back: an epigenetic memory for autophagy

González-Rodríguez, P., Füllgrabe, J., & Joseph, B. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01159-4 · Cited by 44

Activation of polyamine catabolism promotes glutamine metabolism and creates a targetable vulnerability in lung cancer

Han, X., Wang, D., Liao, Y., Wang, N., Shen, J., Wang, J., Zhang, L., Chen, L., Gao, S., Zong, W., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2319429121 · Cited by 46

The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease

Finney, A. C., Das, S., Kumar, D., McKinney, M. P., Cai, B., Yurdagul, A., & Rom, O. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1116861 · Cited by 40

An mTOR siRNA‐Loaded Spermidine/DNA Tetrahedron Nanoplatform with a Synergistic Anti‐Inflammatory Effect on Acute Lung Injury

Huang, C., You, Q., Xu, J., Wu, D., Chen, H., Guo, Y., Xu, J., Hu, M., & Qian, H. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202200008 · Cited by 40

Stress triggers irritable bowel syndrome with diarrhea through a spermidine-mediated decline in type I interferon.

Zhang, L., Wang, H.-L., Zhang, Y.-F., Mao, X.-T., Wu, T., Huang, Z.-H., Jiang, W.-J., Fan, K.-Q., Liu, D.-D., Yang, B., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.09.002 · Cited by 40

A reciprocal regulation of spermidine and autophagy in podocytes maintains the filtration barrier

Liang, W., Yamahara, K., Hernando-Erhard, C., Lagies, S., Wanner, N., Liang, H., Schell, C., Kammerer, B., Huber, T. B., & Bork, T. (2020) · Kidney International · doi:10.1016/j.kint.2020.06.016 · Cited by 39

Novel aspects of age-protection by spermidine supplementation are associated with preserved telomere length

Wirth, A., Wolf, B., Huang, C.-K., Glage, S., Hofer, S. J., Bankstahl, M., Bär, C., Thum, T., Kahl, K. G., Sigrist, S. J., et al. (2021) · GeroScience · doi:10.1007/s11357-020-00310-0 · Cited by 47

Chemical activation of SAT1 corrects diet-induced metabolic syndrome

Castoldi, F., Hyvönen, M. T., Durand, S., Aprahamian, F., Sauvat, A., Malik, S. A., Baracco, E. E., Vacchelli, E., Opolon, P., Signolle, N., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0550-z · Cited by 39

Rapamycin maintains NAD+/NADH redox homeostasis in muscle cells

Zhang, Z., Xu, H. N., Li, S., Dávila, A., Chellappa, K., Davis, J. G., Guan, Y., Frederick, D. W., Chu, W., Zhao, H., et al. (2020) · Aging · doi:10.18632/aging.103954 · Cited by 40

Spermidine ameliorates liver ischaemia-reperfusion injury through the regulation of autophagy by the AMPK-mTOR-ULK1 signalling pathway

Liu, H., Dong, J., Song, S., Zhao, Y., Wang, J., Fu, Z., & Yang, J. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.08.162 · Cited by 38

Role of mitophagy in the neurodegenerative diseases and its pharmacological advances: A review

Wang, Q., Xue, H., Yue, Y., Hao, S., Huang, S., & Zhang, Z. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1014251 · Cited by 38

Lighting up arginine metabolism reveals its functional diversity in physiology and pathology

Li, R., Li, Y., Jiang, K., Zhang, L., Li, T., Zhao, A., Zhang, Z., Xia, Y., Ge, K., Chen, Y., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.09.011 · Cited by 41

Gut Microbiota-Derived Metabolites in Atherosclerosis: Pathways, Biomarkers, and Targets

Tonch-Cerbu, A.-K., Boicean, A., Stoia, O., & Teodoru, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178488 · Cited by 46

Studying Huntington’s Disease in Yeast: From Mechanisms to Pharmacological Approaches

Hofer, S. J., Kainz, K., Zimmermann, A., Bauer, M. A., Pendl, T., Poglitsch, M., Madeo, F., & Carmona‐Gutiérrez, D. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00318 · Cited by 41

1,1′-binaphthyl-2,2′-diamine as a novel MALDI matrix to enhance the in situ imaging of metabolic heterogeneity in lung cancer

Sun, C., Liu, W., Mu, Y., & Wang, X. D. (2019) · Talanta · doi:10.1016/j.talanta.2019.120557 · Cited by 38

Spermidine Suppresses Development of Experimental Abdominal Aortic Aneurysms

Liu, S., Huang, T., Liu, R., Cai, H., Pan, B., Liao, M., Yang, P., Wang, L., Huang, J., Ge, Y., et al. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.014757 · Cited by 38

Caloric restriction mimetics for the treatment of cardiovascular diseases

Sciarretta, S., Forte, M., Castoldi, F., Frati, G., Versaci, F., Sadoshima, J., Kroemer, G., & Maiuri, M. C. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa297 · Cited by 39

Targeting the Mitochondria-Proteostasis Axis to Delay Aging

Zimmermann, A., Madreiter‐Sokolowski, C. T., Stryeck, S., & Abdellatif, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.656201 · Cited by 42

TIP60 in aging and neurodegeneration

Li, Z., & Rasmussen, L. J. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101195 · Cited by 37

METTL3-IGF2BP3-axis mediates the proliferation and migration of pancreatic cancer by regulating spermine synthase m6A modification

Guo, Z., Zhang, X., Lin, C., Huang, Y., Zhong, Y., Guo, H., Zhou, Z., & Weng, S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.962204 · Cited by 37

The role of mitochondrial dysfunction in the pathogenesis of Alzheimer’s disease and future strategies for targeted therapy

Li, X., Wu, Z., Si, X., Li, J., Wu, G., & Wang, M. (2025) · European journal of medical research · doi:10.1186/s40001-025-02699-w · Cited by 44

Mitochondrial DNA Mutation, Diseases, and Nutrient-Regulated Mitophagy

Yang, X., Zhang, R., Nakahira, K., & Gu, Z. (2019) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082018-124643 · Cited by 37

The multifaceted roles of natural products in mitochondrial dysfunction

Chen, Q., Ruan, D., Shi, J., Du, D., & Bian, C. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1093038 · Cited by 39

Mitochondrion: A bridge linking aging and degenerative diseases

Zhang, L., Wu, J., Zhu, Z., He, Y., & Fang, R. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121666 · Cited by 38

Guizhi Shaoyao Zhimu Decoction ameliorates gouty arthritis in rats via altering gut microbiota and improving metabolic profile

Bian, M., Zhu, C., Nie, A., & Zhou, Z. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155800 · Cited by 36

The Autophagy Inducer Spermidine Protects Against Metabolic Dysfunction During Overnutrition

Liao, C., Kummert, O. M. P., Bair, A. M., Alavi, N., Alavi, J., Miller, D. M., Bagga, I., Schempf, A. M., Hsu, Y.-M., Woods, B. D., et al. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab145 · Cited by 34

Mitochondrial disease, mitophagy, and cellular distress in methylmalonic acidemia

Luciani, A., Denley, M. C. S., Govers, L. P., Sorrentino, V., & Froese, D. S. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03934-3 · Cited by 41

Spermidine Ameliorates Nonalcoholic Steatohepatitis through Thyroid Hormone-Responsive Protein Signaling and the Gut Microbiota-Mediated Metabolism of Bile Acids

Ni, Y., Hu, Y., Lou, X., Rong, N., Liu, F., Yang, C., Zheng, A., Yang, S. T., Bao, J., & Fu, Z. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c02729 · Cited by 38

Acetone immersion enhanced MALDI-MS imaging of small molecule metabolites in biological tissues

Sun, C., Li, Z., Ma, C., Zang, Q., Li, J., Liu, W., Zhao, H., & Wang, X. (2019) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2019.112797 · Cited by 36

In vitro digestion of spermidine and amino acids in fresh and processed Agaricus bisporus mushroom

dos Reis, G. C. L., Paula, B. M. D., Tavano, O. L., Guidi, L. R., Godoy, H. T., & Glória, M. B. A. (2020) · Food Research International · doi:10.1016/j.foodres.2020.109616 · Cited by 35

Metabolic adaptation to calorie restriction

Guijas, C., Montenegro-Burke, J. R., Cintrón-Colón, R., Domingo-Almenara, X., Sánchez-Alavez, M., Aguirre, C., Shankar, K., Majumder, E. L. ‐., Billings, E., Conti, B., et al. (2020) · Science Signaling · doi:10.1126/scisignal.abb2490 · Cited by 39

The Aged Intestine: Performance and Rejuvenation

Wang, Q., Qi, Y., Shen, W., Xu, J., Wang, L., Chen, S., Hou, T., & Si, J. (2021) · Aging and Disease · doi:10.14336/ad.2021.0202 · Cited by 36

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms

Prasher, P., Sharma, M., Singh, S. K., Gulati, M., Chellappan, D. K., Rajput, R., Gupta, G., Ydyrys, A., Kulbayeva, M., Razis, A. F. A., et al. (2023) · Frontiers in Chemistry · doi:10.3389/fchem.2023.1164477 · Cited by 40

Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease

Park, D. G., Kang, W., Shin, I.-J., Chalita, M., Oh, H.-S., Hyun, D.-W., Kim, H., Chun, J., An, Y.-S., Lee, E. J., et al. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106655 · Cited by 34

Efflux of N1-acetylspermidine from hepatoma fosters macrophage-mediated immune suppression to dampen immunotherapeutic efficacy

Liu, Z., Wu, C.-Y., Wu, R., Wang, J.-C., Huang, C.-X., Wang, X., Zhang, Y., Zheng, L., Chen, Y., Lao, X., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.05.006 · Cited by 39

Multilevel Metabolic Engineering of Bacillus amyloliquefaciens for Production of the Platform Chemical Putrescine from Sustainable Biomass Hydrolysates

Li, L., Zou, D., Ji, A., He, Y., Liu, Y., Deng, Y., Chen, S., & Wei, X. (2020) · ACS Sustainable Chemistry & Engineering · doi:10.1021/acssuschemeng.9b05484 · Cited by 34

Accumulation of Agmatine, Spermidine, and Spermine in Sprouts and Microgreens of Alfalfa, Fenugreek, Lentil, and Daikon Radish

Cigić, I. K., Rupnik, S., Rijavec, T., Ulrih, N. P., & Cigić, B. (2020) · Foods · doi:10.3390/foods9050547 · Cited by 34

What We Know So Far about the Metabolite-Mediated Microbiota-Intestinal Immunity Dialogue and How to Hear the Sound of This Crosstalk

Caffaratti, C., Plazy, C., Méry, G., Tidjani, A.-R., Fiorini, F., Thiroux, S., Toussaint, B., Hannani, D., & Gouëllec, A. L. (2021) · Metabolites · doi:10.3390/metabo11060406 · Cited by 36

The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration

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A Peptide HEPFYGNEGALR from Apostichopus japonicus Alleviates Acute Alcoholic Liver Injury by Enhancing Antioxidant Response in Male C57BL/6J Mice

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