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- Title
MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.
- Authors
Lee, Dongyeop; An, Seon Woo A.; Jung, Yoonji; Yamaoka, Yasuyo; Ryu, Youngjae; Goh, Grace Ying Shyen; Beigi, Arshia; Yang, Jae-Seong; Jung, Gyoo Yeol; Ma, Dengke K.; Ha, Chang Man; Taubert, Stefan; Lee, Youngsook; Lee, Seung-Jae V.
- 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.
- Subjects
LOW temperatures; SATURATED fatty acids; FATTY acid desaturase; UNSATURATED fatty acids; MONOUNSATURATED fatty acids; LONGEVITY; BODY temperature
- Publication
PLoS Biology, 2019, Vol 17, Issue 8, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.3000415