ArticleCell metabolism2014
Nucleocytosolic depletion of the energy metabolite acetyl-coenzyme a stimulates autophagy and prolongs lifespan.
Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 3 of them syntheses that pooled it.
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Who cites it
158 citing papers in PubMed, 3 syntheses or guidelines pooled it, 251 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Mitochondrial Acetyl-CoA Synthetase 3 is Biosignature of Gastric Cancer Progression.Cancer medicine · 2018Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Metabolic effects of fasting on human and mouse blood in vivo.Autophagy · 2017Trial
- The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism.Nature communications · 2026Article
- Gut microbiota-derived succinate links proteostasis collapse to α-synuclein pathology and aging.iScience · 2026Article
- Histone modifications in biological age determination: mechanisms, biomarkers, and therapeutic perspectives.GeroScience · 2026Review
- Local acetyl-CoA metabolism and acetate recycling as epigenetic regulators of chromatin dynamics.FEMS yeast research · 2026Review
- Changes in the brain [NADFrontiers in aging neuroscience · 2026Review
- NADCells · 2025Review
- Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice.Stem cell research & therapy · 2025Article
- ACOT12, a novel factor in the pathogenesis of kidney fibrosis, modulates ACBD5.Experimental & molecular medicine · 2025Article
- Regulatory Roles for SIRT1 in Aging and Immunosenescence.Results and problems in cell differentiation · 2025Review
- The lifespan-extending MEK1 inhibitor trametinib promotes regulation of de novo lipogenesis enzymes by chaperone-mediated autophagy.Frontiers in aging · 2025Article
- Mechanisms and cross-talk of regulated cell death and their epigenetic modifications in tumor progression.Molecular cancer · 2024Review
- Mendelian randomization analyses support causal relationships between gut microbiome and longevity.Journal of translational medicine · 2024Article
- Aging-induced short-chain acyl-CoA dehydrogenase promotes age-related hepatic steatosis by suppressing lipophagy.Aging cell · 2024Article
- Spermidine is essential for fasting-mediated autophagy and longevity.Nature cell biology · 2024Article
- Structure, function, and lipid sensing activity in the thioesterase superfamily.Biochemical Society transactions · 2024Review
- Socialized mitochondria: mitonuclear crosstalk in stress.Experimental & molecular medicine · 2024Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 7 institutions in 4 countries.
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Abstract
Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status of cells affects both aging and autophagy through as-yet-elusive metabolic circuitries. Here, we show that nucleocytosolic acetyl-coenzyme A (AcCoA) production is a metabolic repressor of autophagy during aging in yeast. Blocking the mitochondrial route to AcCoA by deletion of the CoA-transferase ACH1 caused cytosolic accumulation of the AcCoA precursor acetate. This led to hyperactivation of nucleocytosolic AcCoA-synthetase Acs2p, triggering histone acetylation, repression of autophagy genes, and an age-dependent defect in autophagic flux, culminating in a reduced lifespan. Inhibition of nutrient signaling failed to restore, while simultaneous knockdown of ACS2 reinstated, autophagy and survival of ach1 mutant. Brain-specific knockdown of Drosophila AcCoA synthetase was sufficient to enhance autophagic protein clearance and prolong lifespan. Since AcCoA integrates various nutrition pathways, our findings may explain diet-dependent lifespan and autophagy regulation.
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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.