MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis

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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.
Publisher
PUBLIC LIBRARY SCIENCE
Issue Date
2019-08
Language
English
Article Type
Article
Citation

PLOS BIOLOGY, v.17, no.8

ISSN
1544-9173
DOI
10.1371/journal.pbio.3000415
URI
http://hdl.handle.net/10203/267533
Appears in Collection
BS-Journal Papers(저널논문)
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