ArticleCancer research2017
Spermidine Prolongs Lifespan and Prevents Liver Fibrosis and Hepatocellular Carcinoma by Activating MAP1S-Mediated Autophagy.
Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
100 citing papers in PubMed, 2 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review.Molecules (Basel, Switzerland) · 2020Pooled it
- Trial
- SAT1-Induced Spermidine Depletion Potentiates Food Allergy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association between salivary microbiota-related amino acid metabolic dysregulation and tacrolimus-induced gingival overgrowth following kidney transplantation.BMC oral health · 2026Article
- Links Between Autophagy and Healthy Aging.Journal of molecular biology · 2026Review
- In Vitro Antioxidant and Cellular Activities of Functionalized Spermidine by Conjugating with Ascorbic Acid in Human Skin Cells.Molecules (Basel, Switzerland) · 2026Article
- Lifespan-Extending Endogenous Metabolites.Aging cell · 2026Review
- Polyamine metabolism as a regulator of cellular and organismal aging.Amino acids · 2026Review
- Elaidic acid suppresses hepatocellular carcinoma growth through modulating the production of intestinalInternational journal of biological sciences · 2026Article
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- Cell-specific roles of autophagy in liver fibrosis: implications for targeted pharmacotherapy.Annals of medicine · 2025Review
- Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.Nature cell biology · 2025Article
- Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2025Review
- Protective Role of Spermidine Against Diabetes-Induced Ovarian and Endometrial Injury via LC3 and Beclin-1 Modulation.Antioxidants (Basel, Switzerland) · 2025Article
- Spatial metabolic and phenotypic characterization of the germ-free mouse model.Annals of the New York Academy of Sciences · 2025Article
- Telmisartan reverses hepatic steatosis via PCK1 upregulation: A novel PPAR-independent mechanism in experimental models of MASLD.Pharmacological research · 2025Article
- The Effect of Microbiome-Derived Metabolites in Inflammation-Related Cancer Prevention and Treatment.Biomolecules · 2025Review
- Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.Acta pharmaceutica Sinica. B · 2025Article
- Autophagy in erectile dysfunction: focusing on apoptosis and fibrosis.Asian journal of andrology · 2025Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Liver fibrosis and hepatocellular carcinoma (HCC) have worldwide impact but continue to lack safe, low cost, and effective treatments. In this study, we show how the simple polyamine spermidine can relieve cancer cell defects in autophagy, which trigger oxidative stress-induced cell death and promote liver fibrosis and HCC. We found that the autophagic marker protein LC3 interacted with the microtubule-associated protein MAP1S, which positively regulated autophagy flux in cells. MAP1S stability was regulated in turn by its interaction with the histone deacetylase HDAC4. Notably, MAP1S-deficient mice exhibited a 20% reduction in median survival and developed severe liver fibrosis and HCC under stress. Wild-type mice or cells treated with spermidine exhibited a relative increase in MAP1S stability and autophagy signaling via depletion of cytosolic HDAC4. Extending recent evidence that orally administered spermidine can extend lifespan in mice, we determined that life extension of up to 25% can be produced by lifelong administration, which also reduced liver fibrosis and HCC foci as induced by chemical insults. Genetic investigations established that these observed impacts of oral spermidine administration relied upon MAP1S-mediated autophagy. Our findings offer a preclinical proof of concept for the administration of oral spermidine to prevent liver fibrosis and HCC and potentially extend lifespan.
Indexed as
Identifiers
What OpenQuestion holds
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.