Gene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity

Mota-Martorell, Natalia; Jove, Mariona; Pradas, Irene; Berdún, Rebeca; Sanchez, Isabel; Naudi, Alba; Gari, Eloi; Barja, Gustavo; Pamplona, Reinald

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00210-3) contains supplementary material, which is available to authorized users.