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

Autor: Dongyeop Lee, Seon Woo A An, Yoonji Jung, Yasuyo Yamaoka, Youngjae Ryu, Grace Ying Shyen Goh, Arshia Beigi, Jae-Seong Yang, Gyoo Yeol Jung, Dengke K Ma, Chang Man Ha, Stefan Taubert, Youngsook Lee, Seung-Jae V Lee
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Biology, Vol 17, Iss 8, p e3000415 (2019)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.3000415
Popis: 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.
Databáze: Directory of Open Access Journals
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