ArticleScience advances2024
Ketogenic diet induces p53-dependent cellular senescence in multiple organs.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of Different Exercises Combined with Different Dietary Interventions on Body Composition: A Systematic Review and Network Meta-Analysis.Nutrients · 2024Pooled it
- Digitally enhanced ketogenic diet versus low-fat diet for cardio-renal-metabolic health in a predominantly Hispanic adult population with overweight or obesity: Pilot randomised clinical trial.Diabetes, obesity & metabolism · 2025Trial
- Macronutrient mixtures and interactions in health and disease.Nature reviews. Endocrinology · 2026Review
- A compendium of circulating biomarkers of senescence in humans: Insights on mechanistic impact across health domains and modulation by therapeutic interventions.Ageing research reviews · 2026Review
- Metabolites and cancer metastasis.Oncogene · 2026Review
- Ambient PMEnvironment & health (Washington, D.C.) · 2026Article
- Ketogenic Diet as an Adjuvant in Epithelial Cancers: Mechanisms, Model Systems, and Translational Opportunities.Cancers · 2026Review
- Metabolic Therapy in Glioblastoma-Mapping the Evidence for Ketogenic Diet as an Adjunctive Strategy.Nutrients · 2026Review
- Gut Microbiota, Immunity, and Metabolism in the Progression From Chronic Liver Disease to Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Ketogenic Diet in Obesity and Diabetes: A Narrative Review.Nutrients · 2026Review
- Ketogenic diet exacerbates DSS-induced colitis through a β-hydroxybutyrate-Thomasclavelia spiroformis-γδ17 T cell axis in mice.Nature communications · 2026Article
- Ketogenic diet sex-dependent effects on rat bone marrow cells during development and β-HB protection in hypoglycemia.Scientific reports · 2026Article
- Ketogenic diet and β-hydroxybutyrate inhibit HDAC1 to preserve vascular smooth muscle cell function in thoracic aortic aneurysm.Journal of advanced research · 2026Article
- Comparative analysis of senolytic drugs reveals mitochondrial determinants of efficacy and resistance.Nature aging · 2026Article
- Metabolic reprogramming in diabetes and other endocrine and metabolic disorders: exploring the Warburg effect, ketones, and SGLT2 inhibitors.Reviews in endocrine & metabolic disorders · 2026Review
- Invited: Longitudinal Assessment of Diets with Varying Carbohydrate-to-Fat Ratios and Fiber Supplementation on Immunometabolic Markers, Liver Function, and Gut Microbiome.The Journal of nutrition · 2026Article
- Review
- A narrative review of dietary patterns in cardiovascular-kidney-metabolic syndrome.Frontiers in nutrition · 2026Review
- Ketogenic interventions enhance REM sleep in females and support memory in aged rats.Frontiers in aging neuroscience · 2026Article
- Sucrose-free low-fat diet induces metabolic dysfunction through gut dysbiosis and colonic inflammation in mice.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.
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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.