한빛사 논문
Dongyeop Lee1,†,‡, Seon Woo A. An2,†, Yoonji Jung2,†, Yasuyo Yamaoka3, Youngjae Ryu4, Grace Ying Shyen Goh5, Arshia Beigi5, Jae-Seong Yang6, Gyoo Yeol Jung6,7, Dengke K. Ma8, Chang Man Ha4, Stefan Taubert5, Youngsook Lee1,3, Seung-Jae V. Lee2,*
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea, 2Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon, South Korea, 3Department of Integrative Bioscience & Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea, 4Research Division and Brain Research Core Facilities, Korea Brain Research Institute, Daegu, South Korea, 5Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, Department of Medical Genetics, University of
British Columbia, Vancouver, British Columbia, Canada, 6Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea, 7School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea, 8Cardiovascular Research Institute and Department of Physiology, University of California San Francisco, San Francisco, California, United States of America
†These authors contributed equally to this work.
‡Current address: Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
*Corresponding author
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.
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