RRC ID 59530
Author Lee D, An SWA, Jung Y, Yamaoka Y, Ryu Y, Goh GYS, Beigi A, Yang JS, Jung GY, Ma DK, Ha CM, Taubert S, Lee Y, Lee SV.
Title MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.
Journal PLoS Biol
Abstract Low temperatures delay aging and promote longevity in many organisms. However, the metabolic and homeostatic aspects of low-temperature-induced longevity remain poorly understood. Here, we show that lipid homeostasis regulated by Caenorhabditis elegans Mediator 15 (MDT-15 or MED15), a transcriptional coregulator, is essential for low-temperature-induced longevity and proteostasis. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase that converts saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), at low temperatures. We then demonstrate that maintaining a high UFA/SFA ratio is essential for proteostasis at low temperatures. We show that dietary supplementation with a monounsaturated fatty acid, oleic acid (OA), substantially mitigates the short life span and proteotoxicity in mdt-15(-) animals at low temperatures. Thus, lipidostasis regulated by MDT-15 appears to be a limiting factor for proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of lipid regulation in maintaining normal organismal physiology under different environmental conditions.
Volume 17(8)
Pages e3000415
Published 2019-8-1
DOI 10.1371/journal.pbio.3000415
PMID 31408455
PMC PMC6692015
MeSH Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Cold Temperature Dietary Supplements Fatty Acid Desaturases / metabolism Homeostasis Lipid Metabolism Longevity / physiology* Oleic Acid / administration & dosage Proteostasis Transcription Factors / metabolism* Transcriptional Activation
IF 8.386
Times Cited 7
C.elegans tm2182 tm331 tm3410