Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men.

Marine Gueugneau,Jean-Claude Barthélémy,Daniel Béchet,Daniel Taillandier,Cécile Coudy-Gandilhon,Cécile Polge,Christophe Chambon,Julien Verney,Lydie Combaret,Frédéric Roche,Stéphane Walrand,Léonard Féasson

doi:10.3390/ijms22084205

Abstract

(1) 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. (2) 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. (3) 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. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.

Highlights

Aging affects most tissues and physiologic functions, but one of the most affected organs is the skeletal muscle
Our proteomic analysis indicates that aging and metabolic syndrome in men are associated with disturbance in muscle energy metabolism, including phosphocreatine shuttle, anaerobic glycolysis, NADH/NAD+ shuttle, and lipid metabolism
Our previous analysis of muscle histology [17,22], combined with the present investigation of the muscle transcriptome and proteome, provide an integrated view of muscle healthy aging in men and further identify some specific alterations associated with metabolic syndrome

Summary

Introduction

Aging affects most tissues and physiologic functions, but one of the most affected organs is the skeletal muscle. Between the ages of 20 and 80 years, the cross-sectional area of the vastus lateralis muscle may be reduced by up to 40% [1,2]. This progressive decline in muscle mass and function (referred to as sarcopenia) contributes to both loss of autonomy and increased prevalence for frailty. Age-related loss in skeletal muscle contractile strength increases the risk of impaired mobility, falls, and loss of autonomy. Age-related loss of muscle mass triggers severe metabolic side effects, including metabolic syndrome and frailty in the elderly

Methods

Results

Conclusion