MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis
MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis
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DOI：
10.1371/journal.pbio.3000415
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发表时间：
2019-08-01
期刊：
影响因子：
9.8
通讯作者：
Lee, Seung-Jae, V
中科院分区：
文献类型：
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作者：
Lee, Dongyeop;An, Seon Woo A.;Lee, Seung-Jae, V
低温延缓衰老，促进许多生物体的长寿。然而，低温诱导的长寿的代谢和稳态方面仍然知之甚少。在这里，我们表明，脂质稳态调节秀丽隐杆线虫介体15（MDT-15或MED 15），转录辅助调节，是必不可少的低温诱导的寿命和蛋白质平衡。我们发现，抑制mdt-15会阻止动物在低温下长寿。我们发现，MDT-15上调脂肪-7，脂肪酸去饱和酶，在低温下将饱和脂肪酸（SFA）转化为不饱和脂肪酸（UFA）。然后，我们证明，保持高的乌法/SFA的比例是必不可少的蛋白质在低温下。我们发现，饮食中补充一种单不饱和脂肪酸，油酸（OA），大大减轻了低温下mdt-15（-）动物的短寿命和蛋白毒性。因此，MDT-15调节的蛋白质稳态似乎是低温下蛋白质稳态和寿命的限制因素。我们的研究结果强调了脂质调节在不同环境条件下维持正常生物生理学的关键作用。
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.