RRC ID |
59530
|
著者 |
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.
|
タイトル |
MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.
|
ジャーナル |
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.
|
巻・号 |
17(8)
|
ページ |
e3000415
|
公開日 |
2019-8-1
|
DOI |
10.1371/journal.pbio.3000415
|
PII |
PBIOLOGY-D-19-00761
|
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
|
引用数 |
7
|
リソース情報 |
線虫 |
tm2182
tm331
tm3410 |