ArticleProceedings of the National Academy of Sciences of the United States of America2022
PAHSAs reduce cellular senescence and protect pancreatic beta cells from metabolic stress through regulation of Mdm2/p53.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Fatty acid esters of hydroxy fatty acids and alkyl-diacylglycerols: minor but bioactive components in human milk.Biochemical Society transactions · 2026Review
- ATGL-catalyzed biosynthesis mediates the upregulation of fatty acid hydroxy fatty acids (FAHFA) levels in white adipose tissue with fasting.The Journal of biological chemistry · 2026Article
- seneR: An R package for comprehensive senescence assessment and its application in type 2 diabetes and osteoarthritis.Computational and structural biotechnology journal · 2026Article
- Senotherapeutics for metabolic disease and diabetic complications.Journal of internal medicine · 2026Review
- Circulating senescence-associated secretory phenotype factors across the stages of type 1 diabetes in a cross-sectional cohort.Scientific reports · 2025Article
- Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.International journal of molecular sciences · 2025Review
- Autoreactive T Cells and Cytokine Stress Drive β-Cell Senescence Entry and Accumulation in Type 1 Diabetes.Diabetes · 2025Article
- Insulin resistance in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- Taurine Alleviates Pancreatic β-Cell Senescence by Inhibition of p53 Pathway.Journal of diabetes · 2025Article
- The measurement, regulation and biological activity of FAHFAs.Nature chemical biology · 2025Review
- Pyruvate Carboxylase as a Moonlighting Metabolic Enzyme Protects β-Cell From Senescence.Journal of diabetes · 2025Article
- AIG1 protects against doxorubicin-induced cardiomyocyte ferroptosis and cardiotoxicity by promoting ubiquitination-mediated p53 degradation.Theranostics · 2025Article
- Investigating the Pathogenesis and Treatment of Type 2 Diabetes from the Perspective of Adipose Tissue.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- SenNet recommendations for detecting senescent cells in different tissues.Nature reviews. Molecular cell biology · 2024Review
- Safeguarding genomic integrity in beta-cells: implications for beta-cell differentiation, growth, and dysfunction.Biochemical Society transactions · 2024Review
- The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Beneficial metabolic effects of PAHSAs depend on the gut microbiota in diet-induced obese mice but not in chow-fed mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
- Clinical efficacy of the fourth dose of the BNT162b2 vaccine in maintenance dialysis patients.Journal of nephrology · 2023Article
- Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Senescence in pancreatic beta cells plays a major role in beta cell dysfunction, which leads to impaired glucose homeostasis and diabetes. Therefore, prevention of beta cell senescence could reduce the risk of diabetes. Treatment of nonobese diabetic (NOD) mice, a model of type 1 autoimmune diabetes (T1D), with palmitic acid hydroxy stearic acids (PAHSAs), a novel class of endogenous lipids with antidiabetic and antiinflammatory effects, delays the onset and reduces the incidence of T1D from 82% with vehicle treatment to 35% with PAHSAs. Here, we show that a major mechanism by which PAHSAs protect islets of the NOD mice is by directly preventing and reversing the initial steps of metabolic stress-induced senescence. In vitro PAHSAs increased Mdm2 expression, which decreases the stability of p53, a key inducer of senescence-related genes. In addition, PAHSAs enhanced expression of protective genes, such as those regulating DNA repair and glutathione metabolism and promoting autophagy. We demonstrate the translational relevance by showing that PAHSAs prevent and reverse early stages of senescence in metabolically stressed human islets by the same Mdm2 mechanism. Thus, a major mechanism for the dramatic effect of PAHSAs in reducing the incidence of type 1 diabetes in NOD mice is decreasing cellular senescence; PAHSAs may have a similar benefit in humans.
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