ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2021
The Autophagy Inducer Spermidine Protects Against Metabolic Dysfunction During Overnutrition.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Dietary Spermidine Mitigates Radiation-Induced Intestinal Injury by Reshaping the Microbiota-Barrier-Inflammation Axis.Food science & nutrition · 2026Article
- 4-Hydroxybenzyl Alcohol Mitigates Hyperlipidemia-Associated Depression by Inhibiting Neuroinflammation via the NKIRAS2/NF-κB Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dietary pyrroloquinoline quinone and spermidine in healthy longevity: targeting the hallmarks of aging.Frontiers in aging · 2026Review
- Fabricating Microfluidic Co-Cultures of Immortalized Cell Lines Uncovers Robust Design Principles for the Simultaneous Formation of Patterned, Vascularized, and Stem Cell-Derived Adipose Tissue.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Interplay between ALK2Cell death discovery · 2025Article
- Spermidine as a Potential Protective Agents Against Poly(I:C)-Induced Immune Response, Oxidative Stress, Apoptosis, and Testosterone Decrease in Yak Leydig Cells.International journal of molecular sciences · 2025Article
- The Yeast-Fermented Garlic and a Balance of Spermine/Spermidine Activates Autophagy via EGR1 Transcriptional Factor.Molecular nutrition & food research · 2025Article
- Natural Polyamine Spermidine Inhibits the In Vitro Oxidation of LDL.Molecules (Basel, Switzerland) · 2025Article
- Autophagy in Muscle Regeneration: Mechanisms, Targets, and Therapeutic Perspective.International journal of molecular sciences · 2024Review
- Spermidine-Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.Kidney diseases (Basel, Switzerland) · 2023Review
- Identification of adipose tissue transcriptomic memory of anorexia nervosa.Molecular medicine (Cambridge, Mass.) · 2023Article
- Molecular targets of spermidine: implications for cancer suppression.Cell stress · 2023Article
- Relating aging and autophagy: a new perspective towards the welfare of human health.EXCLI journal · 2023Review
- Nutrition Strategies Promoting Healthy Aging: From Improvement of Cardiovascular and Brain Health to Prevention of Age-Associated Diseases.Nutrients · 2022Review
- Spermidine rejuvenates T lymphocytes and restores anticancer immunosurveillance in aged mice.Oncoimmunology · 2022Article
- Targeting Cardiovascular Risk Factors Through Dietary Adaptations and Caloric Restriction Mimetics.Frontiers in nutrition · 2021Review
Corrections and comments
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Authors and funding
20 authors at 1 institution in 2 countries.
Funding
Abstract
Autophagy, a process catabolizing intracellular components to maintain energy homeostasis, impacts aging and metabolism. Spermidine, a natural polyamine and autophagy activator, extends life span across a variety of species, including mice. In addition to protecting cardiac and liver tissue, spermidine also affects adipose tissue through unexplored mechanisms. Here, we examined spermidine in the links between autophagy and systemic metabolism. Consistently, daily injection of spermidine delivered even at late life is sufficient to cause a trend in life-span extension in wild-type mice. We further found that spermidine has minimal metabolic effects in young and old mice under normal nutrition. However, spermidine counteracts high-fat diet (HFD)-induced obesity by increasing lipolysis in visceral fat. Mechanistically, spermidine increases the hepatokine fibroblast growth factor 21 (FGF21) expression in liver without reducing food intake. Spermidine also modulates FGF21 in adipose tissues, elevating FGF21 expression in subcutaneous fat, but reducing it in visceral fat. Despite this, FGF21 is not required for spermidine action, since Fgf21-/- mice were still protected from HFD. Furthermore, the enhanced lipolysis by spermidine was also independent of autophagy in adipose tissue, given that adipose-specific autophagy-deficient (Beclin-1flox/+Fabp4-cre) mice remained spermidine-responsive under HFD. Our results suggest that the metabolic effects of spermidine occur through systemic changes in metabolism, involving multiple mechanistic pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.