Reduced ech-6 Expression Attenuates Fat-induced Premature Aging in C. elegans
Reduced ech-6 Expression Attenuates Fat-induced Premature Aging in C. elegans
SUMMARY Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans, while a basal expression of ech-6 was important for survival under normal dietary conditions. Lipidomics revealed that supplementation of fat in ech-6-silenced worms had marginal effects on lipid profiles, suggesting an alternative fat utilization for energy production. Transcriptomics further suggest a causal relation between the lysosomal pathway, energy production, and the longevity effect conferred by the interaction between ech-6 and high-fat diets. Indeed, enhancing energy production from endogenous fat by overexpressing lysosomal lipase lipl-4 recapitulated the lifespan effects of high-fat diets on ech-6-silenced worms. Collectively, these results reveal that the gene ech-6 modulates metabolic flexibility and may be a target for promoting metabolic health and longevity.
Jongejan Aldo、Panneman Daan M.、van Weeghel Michel、Smith Reuben L.、Gao Arwen W.、Lapierre Louis R.、Vaz Fr¨|d¨|ric M.、Liu Yasmine J.、Silvestrini Melissa J.、Janssens Georges E.、Houtkooper Riekelt H.、MacInnes Alyson W.
Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam UMC, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam||Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Amalia Children?ˉs HospitalLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam||Core Facility Metabolomics, Amsterdam University Medical Centers, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam||Laboratory of Integrative Systems Physiology, Institute of Bioengineering, ¨|cole Polytechnique F¨|d¨|rale de LausanneDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown UniversityLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam||Core Facility Metabolomics, Amsterdam University Medical Centers, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamDepartment of Molecular Biology, Cell Biology and Biochemistry, Brown UniversityLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam
生物科学现状、生物科学发展分子生物学生物化学
Lifespanech-6metabolic flexibilityhigh-fat dietslysosomelipidomics
Jongejan Aldo,Panneman Daan M.,van Weeghel Michel,Smith Reuben L.,Gao Arwen W.,Lapierre Louis R.,Vaz Fr¨|d¨|ric M.,Liu Yasmine J.,Silvestrini Melissa J.,Janssens Georges E.,Houtkooper Riekelt H.,MacInnes Alyson W..Reduced ech-6 Expression Attenuates Fat-induced Premature Aging in C. elegans[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/2020.11.02.364760.点此复制
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