MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.
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 transcriptiona...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-08-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000415 |
| _version_ | 1819109767366311936 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Dongyeop Lee |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T03:31:03Z |
| format | Article |
| id | doaj.art-a87c878b580e45cd83bfa66a2646930b |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-22T03:31:03Z |
| publishDate | 2019-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-a87c878b580e45cd83bfa66a2646930b2022-12-21T18:40:31ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-08-01178e300041510.1371/journal.pbio.3000415MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.Dongyeop LeeSeon Woo A AnYoonji JungYasuyo YamaokaYoungjae RyuGrace Ying Shyen GohArshia BeigiJae-Seong YangGyoo Yeol JungDengke K MaChang Man HaStefan TaubertYoungsook LeeSeung-Jae V LeeLow 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.https://doi.org/10.1371/journal.pbio.3000415 |
| spellingShingle | 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 MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. PLoS Biology |
| title | MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. |
| title_full | MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. |
| title_fullStr | MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. |
| title_full_unstemmed | MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. |
| title_short | MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis. |
| title_sort | mdt 15 med15 permits longevity at low temperature via enhancing lipidostasis and proteostasis |
| url | https://doi.org/10.1371/journal.pbio.3000415 |
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