Department of Experimental Medicine, University of Lleida-Lleida Biomedical Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain.
Proteomics and Genomics Unit, University of Lleida, 25198, Lleida, Catalonia, Spain.
Geroscience. 2020 Aug;42(4):1157-1173. doi: 10.1007/s11357-020-00210-3. Epub 2020 Jun 23.
Species longevity varies significantly across animal species, but the underlying molecular mechanisms remain poorly understood. Recent studies and omics approaches suggest that phenotypic traits of longevity could converge in the mammalian target of rapamycin (mTOR) signalling pathway. The present study focuses on the comparative approach in heart tissue from 8 mammalian species with a ML ranging from 3.5 to 46 years. Gene expression, protein content, and concentration of regulatory metabolites of the mTOR complex 1 (mTORC1) were measured using droplet digital PCR, western blot, and mass spectrometry, respectively. Our results demonstrate (1) the existence of differences in species-specific gene expression and protein content of mTORC1, (2) that the achievement of a high longevity phenotype correlates with decreased and inhibited mTORC1, (3) a decreased content of mTORC1 activators in long-lived animals, and (4) that these differences are independent of phylogeny. Our findings, taken together, support an important role for mTORC1 downregulation in the evolution of long-lived mammals.
物种的寿命在不同的动物物种之间有很大的差异，但潜在的分子机制仍知之甚少。最近的研究和组学方法表明，长寿的表型特征可能在哺乳动物雷帕霉素靶蛋白（mTOR）信号通路中趋同。本研究专注于从寿命范围为 3.5 至 46 年的 8 种哺乳动物的心脏组织中进行比较分析。使用液滴数字 PCR、western blot 和质谱法分别测量 mTOR 复合物 1（mTORC1）的基因表达、蛋白含量和调节代谢物的浓度。我们的结果表明：（1）存在物种特异性 mTORC1 基因表达和蛋白含量的差异；（2）实现高长寿表型与 mTORC1 的减少和抑制相关；（3）长寿动物中 mTORC1 激活剂的含量降低；（4）这些差异与系统发育无关。综合这些发现，支持了 mTORC1 下调在长寿哺乳动物进化中的重要作用。
