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

Simple item page
dc.contributor.authorMota Martorell, Natàlia
dc.contributor.authorJové Font, Mariona
dc.contributor.authorPradas Barriga, Irene
dc.contributor.authorBerdún Hernández, Rebeca
dc.contributor.authorSanchez, Isabel
dc.contributor.authorNaudí i Farré, Alba
dc.contributor.authorGarí Marsol, Eloi
dc.contributor.authorBarja, Gustavo
dc.contributor.authorPamplona Gras, Reinald
dc.date.accessioned2021-10-20T07:05:21Z
dc.date.available2021-10-20T07:05:21Z
dc.date.issued2020-08-01
dc.date.updated2021-10-20T07:05:21Z
dc.description.abstractMaximum 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.
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (grant number PI14/00328), the Spanish Ministry of Science, Innovation and Universities (RTI2018-099200-B-I00), and the Generalitat of Catalonia, Agency for Management of University and Research Grants (2017SGR696) and Department of Health (SLT002/16/00250) to R.P. This study has been co-financed by FEDER funds from the European Union (“A way to build Europe”).
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1007/s11357-020-00210-3
dc.identifier.idgrec030535
dc.identifier.issn2509-2715
dc.identifier.urihttp://hdl.handle.net/10459.1/72111
dc.language.isoeng
dc.publisherSpringer
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-099200-B-I00/ES/NEUROLIPIDOMICA DEL ENVEJECIMIENTO CEREBRAL HUMANO/
dc.relation.isformatofVersió preprint del document publicat a: https://doi.org/10.1007/s11357-020-00210-3
dc.relation.ispartofGeroscience, 2020, vol. 42, núm. 4, p. 1157-1173
dc.rights(c) Springer, 2020
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.subjectArginine
dc.subjectDroplet digital PCR
dc.subjectFKBP12
dc.subjectLeucine
dc.subjectLongevity
dc.subjectMass spectrometry
dc.subjectMetabolomics
dc.subjectMethionine cycle metabolites
dc.subjectmTOR
dc.subjectPhylogeny
dc.subjectPRAS40
dc.subjectRaptor
dc.subjectWestern blot
dc.titleGene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity
dc.title.alternativemTORC1 and longevit
dc.typeinfo:eu-repo/semantics/article
dc.type.versionsubmittedVersion
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
030535.pdf
Size:
2.1 MB
Format:
Adobe Portable Document Format
Description:
Preprint
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Articles publicats (Ciències Mèdiques Bàsiques)
Articles publicats (IRBLleida)
Articles publicats (Medicina Experimental)
Publicacions de projectes de recerca del Plan Nacional