Sarcopenia: investigation of metabolic changes and its associated mechanisms

Abstract

Background Sarcopenia is one of the most predominant musculoskeletal diseases of the elderly, defined as age-related progressive and generalized loss of muscle mass with a simultaneous reduction in muscle strength and/or function. Using metabolomics, we aimed to examine the association between sarcopenia and the plasma metabolic profile of sarcopenic patients, measured using a targeted HPLC-MS/MS platform. Methods Plasma samples from 22 (17 men) hip fracture patients undergoing surgery (8 sarcopenic, age 81.4+6.3, and 14 non-sarcopenic, age 78.4±8.1) were analyzed. T test, fold change, orthogonal partial least squares discriminant analysis, and sparse partial least squares discriminant analysis were used for mining significant features. Metabolite set enrichment analysis and mediation analysis by PLSSEM were thereafter performed. Results Using a univariate analysis for sarcopenia z score, the amino acid citrulline was the only metabolite with a significant group difference after FDR correction. Positive trends were observed between the sarcopenia z score and very long-chain fatty acids as well as dicarboxylic acid carnitines. Multivariate analysis showed citrulline, non-esterified fatty acid 26:2, and decanedioyl carnitine as the top three metabolites according to the variable importance in projection using oPLS-DA and loadings weight by sPLS-DA. Metabolite set enrichment analysis showed carnitine palmitoyltransferase deficiency (II) as the highest condition related to the metabolome. Conclusions We observed a difference in the plasma metabolic profile in association with different measures of sarcopenia, which identifies very long-chain fatty acids, Carn.DC and citrulline as key variables associated with the disease severity. These findings point to a potential link between sarcopenia and mitochondrial dysfunction and portraits a number of possible biochemical pathways which might be involved in the disease pathogenesis.

Association between F2-Isoprostane Metabolites and Weight Change in Older Women: A Longitudinal Analysis

“…acids and dicarboxylic acid carnitines as key variables associated with disease severity in patients with sarcopenia [42]. These findings combined with our results suggest a potential link between sarcopenia and dysregulation of peroxisomal β-oxidation.…”

“…β-oxidation of very long-chain fatty acids (VLC-FA) and subsequent production of dicarboxylic acid carnitines also occur in the peroxisome [41]. Metabolomic studies identified very long-chain fatty acids and dicarboxylic acid carnitines as key variables associated with disease severity in patients with sarcopenia [42]. These findings combined with our results suggest a potential link between sarcopenia and dysregulation of peroxisomal β-oxidation.…”

The causal relationship of human blood metabolites with the components of Sarcopenia: a two-sample Mendelian randomization analysis

“…Acylcarnitine, disrupting peroxisomal or mitochondrial oxidation processes [ 29 ], also plays a part in mitochondrial function, whose dysregulation is highly involved in the pathological loss of skeletal muscle mass and function in the elderly [ 30 ]. 3-dehydrocarnitine is an intermediate in carnitine degradation, and carnitine has been linked to muscle mass or physical weakness [ 31 , 32 ], which plays a crucial role in energy metabolism and mediates the pathway of fatty acid oxidation in the mitochondria [ 33 ]. However, these observational results are limited in determining causal relationships.…”

A prospective longitudinal cohort study on risk factors for COVID-19 vaccination failure (RisCoin): methods, procedures and characterization of the cohort

“…Carnitine and acyl-carnitines were analyzed with an in-house method based on the LC–MS/MS method by Giesbertz et al [ 35 ] and are described by Marques et al [ 36 ].…”