Specific Metabolites Involved in Antioxidation and Mitochondrial Function Are Correlated With Frailty in Elderly Men

Abstract

BackgroundAs an age-related syndrome, frailty may play a central role in poor health among older adults. Sarcopenia overlaps with the physical domain of frailty, and most existing studies have analyzed the associated factors of frailty and sarcopenia as an isolated state. Perturbations in metabolism may play an important role in the presence of frailty or sarcopenia; however, the metabolites associated with frailty, especially overlapping with sarcopenia remain unclear. In this study, we aimed to explore whether amino acids, carnitines, acylcarnitines and lysophosphatidylcholines, as specific panels, are significantly correlated with frailty, especially overlapping with sarcopenia, to gain insight into potential biomarkers and possible biological mechanisms and to facilitate their management.MethodsWe applied a targeted high-performance liquid chromatography-tandem mass spectrometry approach in serum samples from 246 Chinese older men (age 79.2 ± 7.8 years) with frailty (n = 150), non-frailty (n = 96), frailty and sarcopenia (n = 52), non-frail and non-sarcopenic control (n = 85). Frailty was evaluated using Freid phenotype criteria, sarcopenia was defined by diagnostic algorithm of Asian Working Group on Sarcopenia, and the participants were diagnosed as frailty and sarcopenia when they met the evaluation criteria of both frailty and sarcopenia. A panel of 29 metabolomic profiles was assayed and included different classes of amino acids, carnitines, acylcarnitines, and lysophosphatidylcholines (LPCs). Multivariate logistic regression was used to screen the metabolic factors contributing to frailty status, and orthogonal partial least squares discriminant analysis was used to explore important factors and distinguish different groups.ResultsIn older men demonstrating the frail phenotype, amino acid perturbations included lower tryptophan and higher glycine levels. With regard to lipid metabolism, the frailty phenotype was characterized by lower concentrations of isovalerylcarnitine (C5), LPC16:0 and LPC18:2, while higher levels of octanoyl-L-carnitine (C8), decanoyl-L-carnitine (C10), dodecanoyl-L-carnitine (C12) and tetradecanoyl-L-carnitine (C14). After adjusting for several clinical confounders, tryptophan, LPC18:2, LPC 16:0 and C5 were negatively correlated with frailty, and C8 and C12 were positively related to frailty. We preliminarily identified metabolic profiles (LPC16:0, LPC18:2, glycine and tryptophan) that may distinguish older men with frailty from those without frailty. Importantly, a set of serum amino acids and LPCs (LPC16:0, LPC18:2, and tryptophan) was characterized in the metabotype of older adults with an overlap of frailty and sarcopenia. The metabolites that were most discriminating of frailty status implied that the underlying mechanism might be involved in antioxidation and mitochondrial dysfunction.ConclusionsThese present metabolic analyses may provide valuable information on the potential biomarkers and possible biological mechanisms of frailty, and overlapping sarcopenia. The findings obtained may offer insight into their management in older adults.

Association between sarcopenia and frailty in elderly patients with chronic kidney disease

“…Second, various biomarkers for frailty discovered in metabolomics have chiefly focused on amino acids, 25 while metabolites associated with sarcopenia have not been comprehensively profiled and examined. Meng et al 26 applied a targeted high‐performance liquid chromatography–tandem mass spectrometry approach to distinguish elderly patients with frailty from those without frailty by different characteristic metabotypes and found similar characteristic metabotypes between frailty and F&S patients. With sarcopenia or not does not significantly impact the metabolic characteristics of frailty.…”

The Effect of Metabolites on Mitochondrial Functions in the Pathogenesis of Skeletal Muscle Aging

“…The higher the serum concentration of these metabolites, the worse the physical function of patients with sarcopenia. 17,97 The toxic effects of fatty acids and their acylcarnitine derivatives mainly depend on the saturation and chain length of fatty acids, and thus, saturated long-chain fatty acids are the most lipotoxic. LCFA comprise all fatty acids with more than 12 carbon atoms in the chain, of which palmitic acid and stearic acid and their acylcarnitine derivatives are the most harmful to muscle function.…”

“…Observational studies have shown a significant downward trend in the serum levels of lysophosphatidylcholine (LPC) in patients with sarcopenia, indicating that LPC is one of the characteristic metabolites distinguishing elderly people with and without sarcopenia. 17,97,103 The serum levels of LPCs contributing significantly to this discrimination between elderly people with and without sarcopenia are LPC 16:0, LPC 18:0, and LPC 18:2, which are also the most abundant LPC present in human plasma.…”

Life Expectancy and COVID-19 in Relation to Systemic Endotheliopathy (Systemic Endotheliopathy after COVID-19 as Life Expectancy Indicator: Development, Risk Factors, Prevention)

“…A study in men with frailty syndrome (asthenia) found that the frailty phenotype was characterized by lower concentrations of isovalerylcarnitine, higher levels of octanoyl-L-carnitine, decanoyl-L-carnitine, dodecanoyl-L-carnitine, and tetradecanoyl-Lcarnitine. Metabolic profiles with measurement of glycine and tryptophan levels can distinguish elderly men with frailty from people without frailty 51 . Similar results on the increased risk of developing frailty syndrome in the event of carnitine metabolism disorders were obtained in another study 50 .…”