ArticleNature communications2023
Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 24 citations in OpenAlex.
- Loss of BCAP31 or POLR1E Accelerates Aging in C. elegans and is Linked to Senescence in Vascular Endothelium.Advanced biology · 2026Article
- Trilobatin is associated with reduced lipid accumulation in multiple biological models: insights from transcriptomics, molecular docking, and molecular dynamics simulations.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Autophagy-Independent Function of ATG-18 Is Essential for Gonadal Longevity in Caenorhabditis elegans.Aging cell · 2026Article
- A genetically encoded bifunctional enzyme mitigates redox imbalance and lipotoxicity.Nature metabolism · 2026Article
- Glycerol and Glycerol-3-Phosphate: Multifaceted Metabolites in Metabolism, Cancer, and Other Diseases.Endocrine reviews · 2026Review
- Potential impact of marine heatwaves on the survival and transcriptomic signature of free-living third-stage larvae (L3) ofFrontiers in veterinary science · 2026Article
- Changes in the brain [NADFrontiers in aging neuroscience · 2026Review
- Suppressing Glycerol-3-phosphate Phosphatase and Enhancing Glycerol-3-Phosphate Shuttle Flux Crucial for High-Efficiency Fatty Acid Production in the Fast-Growing Oleaginous Schizochytrium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bacterial exopolysaccharides mediate activation of flavin-containing monooxygenase 2 to extend lifespan in Caenorhabditis elegans.Cell communication and signaling : CCS · 2025Article
- The protein phosphatase 6 subunit SAPS3 modulates lifespan by regulating metabolism.Science advances · 2025Article
- Involvement of NRF2 and AMPK signaling in aging and progeria: a digest.Redox biology · 2025Review
- Review
- An organism-level quantitative flux model of energy metabolism in mice.Cell metabolism · 2025Article
- Transcriptomic Approaches to Investigate the Anti-Aging Effects of Blueberry Anthocyanins in a Caenorhabditis Elegans Aging Model.Antioxidants (Basel, Switzerland) · 2024Article
- Diacylglycerol Kinases and Its Role in Lipid Metabolism and Related Diseases.International journal of molecular sciences · 2024Review
- Essential role of germ cell glycerol-3-phosphate phosphatase for sperm health, oxidative stress control and male fertility in mice.Molecular metabolism · 2024Article
- AMPK: The energy sensor at the crossroads of aging and cancer.Seminars in cancer biology · 2024Review
- Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation.Biomedicines · 2024Review
- Lack ofGenes · 2024Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic stress caused by excess nutrients accelerates aging. We recently demonstrated that the newly discovered enzyme glycerol-3-phosphate phosphatase (G3PP; gene Pgp), which operates an evolutionarily conserved glycerol shunt that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol, counters metabolic stress and promotes healthy aging in C. elegans. However, the mechanism whereby G3PP activation extends healthspan and lifespan, particularly under glucotoxicity, remained unknown. Here, we show that the overexpression of the C. elegans G3PP homolog, PGPH-2, decreases fat levels and mimics, in part, the beneficial effects of calorie restriction, particularly in glucotoxicity conditions, without reducing food intake. PGPH-2 overexpression depletes glycogen stores activating AMP-activate protein kinase, which leads to the HLH-30 nuclear translocation and activation of autophagy, promoting healthy aging. Transcriptomics reveal an HLH-30-dependent longevity and catabolic gene expression signature with PGPH-2 overexpression. Thus, G3PP overexpression activates three key longevity factors, AMPK, the TFEB homolog HLH-30, and autophagy, and may be an attractive target for age-related metabolic disorders linked to excess nutrients.
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