Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Aging (Albany NY). 2022 Aug 30;14(16):6481-6506. doi: 10.18632/aging.204251.
Since interventions such as caloric restriction or fasting robustly promote lipid catabolism and improve aging-related phenotypical markers, we investigated the direct effect of increased lipid catabolism via overexpression of (, FBgn0036449), the major triglyceride hydrolase in on lifespan and physiological fitness. Comprehensive characterization was carried out using RNA-seq, lipidomics and metabolomics analysis. Global overexpression of strongly promoted numerous markers of physiological fitness, including increased female fecundity, fertility maintenance, preserved locomotion activity, increased mitochondrial biogenesis and oxidative metabolism. Increased robustly upregulated the heat shock protein 70 (Hsp70) family of proteins, which equipped the flies with higher resistance to heat, cold, and ER stress via improved proteostasis. Despite improved physiological fitness, overexpression did not extend lifespan. Taken together, these data show that overexpression has broad beneficial effects on physiological fitness, but these effects did not impact lifespan.
由于热量限制或禁食等干预措施能强有力地促进脂肪分解并改善与衰老相关的表型标志物，我们研究了通过过表达（FBgn0036449），即脂肪组织中主要的甘油三酯水解酶，直接增加脂肪分解对寿命和生理适应性的影响。使用 RNA-seq、脂质组学和代谢组学分析进行了全面表征。过表达 强烈促进了许多生理适应性的标志物，包括增加雌性生育力、维持生育能力、保持运动活性、增加线粒体生物发生和氧化代谢。过表达 强烈上调热休克蛋白 70 (Hsp70) 家族蛋白，通过改善蛋白质稳态使果蝇对热、冷和 ER 应激具有更高的抗性。尽管生理适应性得到改善，但 过表达并未延长寿命。总之，这些数据表明，过表达对生理适应性有广泛的有益影响，但这些影响并未影响寿命。
