title: Aging Reduces the Activation of the mTORC1 Pathway after Resistance Exercise and Protein Intake in Human Skeletal Muscle: Potential Role of REDD1 and Impaired Anabolic Sensitivity.
abstract: This study was designed to better understand the molecular mechanisms involved in the anabolic resistance observed in elderly people. Nine young (22 ± 0.1 years) and 10 older (69 ± 1.7 years) volunteers performed a one-leg extension exercise consisting of 10 × 10 repetitions at 70% of their 3-RM, immediately after which they ingested 30 g of whey protein. Muscle biopsies were taken from the vastus lateralis at rest in the fasted state and 30 min after protein ingestion in the non-exercised (Pro) and exercised (Pro+ex) legs. Plasma insulin levels were determined at the same time points. No age difference was measured in fasting insulin levels but the older subjects had a 50% higher concentration than the young subjects in the fed state (p < 0.05). While no difference was observed in the fasted state, in response to exercise and protein ingestion, the phosphorylation state of PKB (p < 0.05 in Pro and Pro+ex) and S6K1 (p = 0.059 in Pro; p = 0.066 in Pro+ex) was lower in the older subjects compared with the young subjects. After Pro+ex, REDD1 expression tended to be higher (p = 0.087) in the older group while AMPK phosphorylation was not modified by any condition. In conclusion, we show that the activation of the mTORC1 pathway is reduced in skeletal muscle of older subjects after resistance exercise and protein ingestion compared with young subjects, which could be partially due to an increased expression of REDD1 and an impaired anabolic sensitivity.
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. marc.francaux@uclouvain.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. benedicte.demeulder@gmail.com.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Demeulder
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. damien.naslain@uclouvain.be.
authors.forename: Damien
authors.initials: D
authors.lastname: Naslain
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. raphael-fortin@hotmail.com.
authors.forename: Raphael
authors.initials: R
authors.lastname: Fortin
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. olivierlutz@msn.com.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lutz
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. gilles.caty@uclouvain.be.
authors.forename: Gilles
authors.initials: G
authors.lastname: Caty
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. louise.deldicque@uclouvain.be.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000368:Aged; D000375:Aging / Q000378:metabolism*; D045930:Anabolic Agents / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005215:Fasting / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism*; D055070:Resistance Training; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D000067816:Whey Proteins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D045930:Anabolic Agents; C469991:DDIT4 protein, human; D007328:Insulin; D046912:Multiprotein Complexes; D014157:Transcription Factors; D000067816:Whey Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: anabolic resistance; autophagy; protein degradation; protein synthesis; sarcopenia