Gene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity
Data de publicació2020-08-01
Pradas Barriga, Irene
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Maximum longevity (ML) varies significantly across animal species, but the underlying molecular mechanisms remain poorly understood. Recent studies and omics approaches suggest that phenotypic traits of ML could to converge in the mammalian target of rapamycin (mTOR) signalling pathway. The present study is a comparative approach using 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 species-specific in gene expression and protein content of mTORC1; 2) that the achievement of a longevity phenotype requires decreased and inhibited mTORC1; 3) decreased content of mTORC1 activators in long-lived animals, and 4) independence of phylogeny relationships on these changes. Altogether, our findings support mTORC1 down-regulation to achieve a longevous phenotype.