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Gene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity.
GeroScience ( IF 5.3 ) Pub Date : 2020-06-23 , DOI: 10.1007/s11357-020-00210-3
Natalia Mota-Martorell 1 , Mariona Jove 1 , Irene Pradas 1 , Rebeca Berdún 1 , Isabel Sanchez 2 , Alba Naudi 1 , Eloi Gari 3 , Gustavo Barja 4 , Reinald Pamplona 1
Affiliation  

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.

中文翻译:

雷帕霉素(mTOR)复合物1的机械靶标的基因表达和调控因子可预测哺乳动物的寿命。

物种寿命在不同动物物种之间差异很大,但对潜在的分子机制仍知之甚少。最近的研究和组学方法表明,长寿的表型性状可以收敛于雷帕霉素(mTOR)信号转导途径的哺乳动物靶标中。本研究的重点是在ML范围从3.5到46岁的8种哺乳动物的心脏组织中进行比较。分别使用液滴数字PCR,蛋白质印迹和质谱法测量mTOR复合物1(mTORC1)的基因表达,蛋白质含量和调节代谢物浓度。我们的研究结果表明(1)mTORC1的物种特异性基因表达和蛋白质含量存在差异;(2)高寿命表型的实现与mTORC1的降低和抑制有关,(3)长寿动物中mTORC1激活剂的含量降低,并且(4)这些差异与系统发育无关。我们的发现加在一起,支持mTORC1下调在长寿哺乳动物进化中的重要作用。
更新日期:2020-06-23
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