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

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Mota Martorell, Natalia and Jové, Mariona and Pradas, Irene and Berdún, Rebeca and Sánchez, Isabel and Naudí, Alba and Gari, Eloi and Barja de Quiroga, Gustavo and Pamplona, Reinald (2020) Gene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity. GeroScience, 42 . 1157–1173. ISSN 2509-2715, ESSN 2509-2723

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Official URL: https://link.springer.com/article/10.1007/s11357-020-00210-3



Abstract

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 longlived mammals.


Item Type:Article
Uncontrolled Keywords:Arginine; FKBP12; Methionine cycle metabolites; mTOR; PRAS40; Raptor
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Mammals
ID Code:62603
Deposited On:16 Oct 2020 08:45
Last Modified:16 Oct 2020 11:39

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