Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men
2021
Gueugneau, Marine | Coudy-Gandilhon, Cécile | Chambon, Christophe | Verney, Julien | Taillandier, Daniel | Combaret, Lydie | Polge, Cécile | Walrand, Stéphane | Roche, Frédéric | Barthélémy, Jean-Claude | Féasson, Léonard | Béchet, Daniel | Unité de Nutrition Humaine (UNH) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA) | Plateforme Exploration du Métabolisme (PFEM) ; Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont ; MetaboHUB-MetaboHUB | Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P) ; Université Clermont Auvergne (UCA)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Auvergne (UFR STAPS - UCA) ; Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA) | Service de Nutrition Clinique [CHU Clermont-Ferrand] ; CHU Gabriel Montpied [Clermont-Ferrand] ; CHU Clermont-Ferrand-CHU Clermont-Ferrand | Biologie Intégrative du Tissu Osseux (LBTO) ; Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Système Nerveux Autonome - Epidémiologie, Physiologie, Ingénierie, Santé (SNA - EPIS) ; Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM) | Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]) | Service de Physiologie Clinique et de l'Exercice [CHU de Saint-Etienne] ; Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)
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Show more [+] Less [-]English. Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men.Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses.Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD+ shuttle and β-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles.Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.
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