Reduced ech-6 Expression Attenuates Fat-induced Premature Aging in C. elegans
Liu, Y. J.; Gao, A. W.; Smith, R. L.; Janssens, G. E.; Panneman, D. M.; Jongejan, A.; van Weeghel, M.; Vaz, F. M.; Silvestrini, M. J.; Lapierre, L. R.; MacInnes, A. W.; Houtkooper, R. H.
Show abstract
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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Ether Lipid Biosynthesis Promotes Lifespan Extension and Enables Diverse Prolongevity Paradigms 97%
- miR-125-chinmo pathway regulates dietary restriction dependent enhancement of lifespan in Drosophila 96%
- Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically-diverse Caenorhabditis nematodes 95%
Similar papers in this journal
- Glycation-lowering compounds inhibit ghrelin signaling to reduce food intake, lower insulin resistance, and extend lifespan. 94%
- Non-canonical Metabolic and Molecular Effects of Calorie Restriction Are Revealed by Varying Temporal Conditions 94%
- Translational regulation of non-autonomous mitochondrial stress response promotes longevity 94%
Similar papers in this journal
- Axin-mediated regulation of lifespan and muscle health in C. elegans involves AMPK-FOXO signaling 95%
- Multi-omics analysis identifies essential regulators of mitochondrial stress response in two wild-type C. elegans strains 95%
- Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.