PMID- 32578071
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20211204
IS  - 2509-2723 (Electronic)
IS  - 2509-2715 (Print)
IS  - 2509-2723 (Linking)
VI  - 42
IP  - 4
DP  - 2020 Aug
TI  - Gene expression and regulatory factors of the mechanistic target of rapamycin 
      (mTOR) complex 1 predict mammalian longevity.
PG  - 1157-1173
LID - 10.1007/s11357-020-00210-3 [doi]
AB  - 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.
FAU - Mota-Martorell, Natalia
AU  - Mota-Martorell N
AD  - Department of Experimental Medicine, University of Lleida-Lleida Biomedical 
      Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain.
FAU - Jove, Mariona
AU  - Jove M
AD  - Department of Experimental Medicine, University of Lleida-Lleida Biomedical 
      Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain.
FAU - Pradas, Irene
AU  - Pradas I
AD  - Department of Experimental Medicine, University of Lleida-Lleida Biomedical 
      Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain.
FAU - Berdun, Rebeca
AU  - Berdun R
AD  - Department of Experimental Medicine, University of Lleida-Lleida Biomedical 
      Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain.
FAU - Sanchez, Isabel
AU  - Sanchez I
AD  - Proteomics and Genomics Unit, University of Lleida, 25198, Lleida, Catalonia, 
      Spain.
FAU - Naudi, Alba
AU  - Naudi A
AD  - Department of Experimental Medicine, University of Lleida-Lleida Biomedical 
      Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain.
FAU - Gari, Eloi
AU  - Gari E
AD  - Department of Basic Medical Sciences, University of Lleida-Lleida Biomedical 
      Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain.
FAU - Barja, Gustavo
AU  - Barja G
AD  - Department of Genetics, Physiology and Microbiology, Complutense University of 
      Madrid (UCM), 28040, Madrid, Spain. gbarja@bio.ucm.es.
FAU - Pamplona, Reinald
AU  - Pamplona R
AD  - Department of Experimental Medicine, University of Lleida-Lleida Biomedical 
      Research Institute (UdL-IRBLleida), 25198, Lleida, Catalonia, Spain. 
      reinald.pamplona@mex.udl.cat.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200623
PL  - Switzerland
TA  - Geroscience
JT  - GeroScience
JID - 101686284
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Gene Expression
MH  - *Longevity/genetics
MH  - Mechanistic Target of Rapamycin Complex 1/genetics
MH  - Phosphorylation
MH  - Regulatory-Associated Protein of mTOR/genetics/metabolism
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC7434991
OTO - NOTNLM
OT  - Arginine
OT  - FKBP12
OT  - Methionine cycle metabolites
OT  - PRAS40
OT  - Raptor
OT  - mTOR
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/06/25 06:00
MHDA- 2021/04/28 06:00
PMCR- 2020/06/23
CRDT- 2020/06/25 06:00
PHST- 2020/01/09 00:00 [received]
PHST- 2020/06/01 00:00 [accepted]
PHST- 2020/06/25 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/06/25 06:00 [entrez]
PHST- 2020/06/23 00:00 [pmc-release]
AID - 10.1007/s11357-020-00210-3 [pii]
AID - 210 [pii]
AID - 10.1007/s11357-020-00210-3 [doi]
PST - ppublish
SO  - Geroscience. 2020 Aug;42(4):1157-1173. doi: 10.1007/s11357-020-00210-3. Epub 2020 
      Jun 23.