Lee, Dongyeop and An, Seon Woo A. and Jung, Yoonji and Yamaoka, Yasuyo and Ryu, Youngjae and Goh, Grace Ying Shyen and Beigi, Arshia and Yang, Jae-Seong and Jung, Gyoo Yeol and Ma, Dengke K. and Ha, Chang Man and Taubert, Stefan and Lee, Youngsook and Lee, Seung-Jae V. and Campisi, Judith (2019) MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. PLOS Biology, 17 (8). e3000415. ISSN 1545-7885
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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.
Item Type: | Article |
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Subjects: | Research Asian Plos > Biological Science |
Depositing User: | Unnamed user with email support@research.asianplos.com |
Date Deposited: | 08 Feb 2023 09:31 |
Last Modified: | 19 Oct 2024 05:41 |
URI: | http://abstract.stmdigitallibrary.com/id/eprint/24 |