MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis
| Autor: | Arshia Beigi, Seung-Jae Lee, Gyoo Yeol Jung, Yasuyo Yamaoka, Dongyeop Lee, Stefan Taubert, Yoonji Jung, Youngjae Ryu, Youngsook Lee, Chang Man Ha, Seon Woo A. An, Dengke K. Ma, Jae-Seong Yang, Grace Y. S. Goh |
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| Přispěvatelé: | Campisi, Judith |
| Rok vydání: | 2019 |
| Předmět: |
Fatty Acid Desaturases
0301 basic medicine Aging Nematoda Physiology Medical and Health Sciences Biochemistry Body Temperature Fats chemistry.chemical_compound RNA interference 0302 clinical medicine Medicine and Health Sciences Homeostasis Biology (General) media_common biology General Neuroscience Fatty Acids Longevity Eukaryota Animal Models Biological Sciences Lipids Cell biology Nucleic acids Cold Temperature Genetic interference Experimental Organism Systems Physiological Parameters Epigenetics General Agricultural and Biological Sciences Research Article Transcriptional Activation QH301-705.5 media_common.quotation_subject Research and Analysis Methods Green Fluorescent Protein General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Model Organisms Genetics Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Nutrition Agricultural and Veterinary Sciences General Immunology and Microbiology Prevention Organisms Biology and Life Sciences Proteins Lipid metabolism Metabolism Lipid Metabolism Invertebrates Luminescent Proteins Oleic acid 030104 developmental biology Proteostasis Fatty acid desaturase Proteotoxicity chemistry Dietary Supplements Animal Studies Caenorhabditis biology.protein RNA Gene expression 030217 neurology & neurosurgery Developmental Biology Oleic Acid Transcription Factors |
| Zdroj: | PLoS Biology PLoS Biology, Vol 17, Iss 8, p e3000415 (2019) PLoS biology, vol 17, iss 8 |
| ISSN: | 1545-7885 |
| 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. Low temperatures delay aging and promote longevity in many organisms. This study shows that at low ambient temperatures, Mediator 15, a transcriptional coregulator, allows the nematode Caenorhabditis elegans to live longer by increasing the levels of unsaturated lipids, helping to maintain protein homeostasis. |
| Databáze: | OpenAIRE |
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