Sarcopenia: recent advances for detection, progression, and metabolic alterations along with therapeutic targets

Abstract

Sarcopenia, a disorder marked by muscle loss and dysfunction, is a global health concern, particularly in aging populations. Sarcopenia is intricately related to various health conditions, including obesity, dysphagia, and frailty, which underscores the complexity. Despite recent advances in metabolomics and other omics data for early detection and treatment, the precise characterization and diagnosis of sarcopenia remains challenging. In the present review we provide an overview of the complex metabolic mechanisms that underlie sarcopenia, with particular emphasis on protein, lipid, carbohydrate, and bone metabolism. The review highlights the importance of leucine and other amino acids in promoting muscle protein synthesis and clarifies the critical role played by amino acid metabolism in preserving muscular health. In addition, the review provides insights regarding lipid metabolism on sarcopenia, with an emphasis on the effects of inflammation and insulin resistance. The development of sarcopenia is largely influenced by insulin resistance, especially with regard to glucose metabolism. Overall, the review emphasizes the complex relationship between bone and muscle health by highlighting the interaction between sarcopenia and bone metabolism. Furthermore, the review outlines various therapeutic approaches and potential biomarkers for diagnosing sarcopenia. These include pharmacological strategies such as hormone replacement therapy and anabolic steroids as well as lifestyle modifications such as exercise, nutrition, and dietary changes.

Keywords: aging; biomarker; exercise; metabolism; sarcopenia.

Fig. 1.

Sarcopenia and associated metabolic dysfunction. The metabolic disturbances were studied at different levels in sarcopenia protein metabolism; decreased blood levels of (BCAAs), particularly leucine, are linked to reduced muscle strength. Tryptophan through its metabolite serotonin can stimulate the expression of myogenic factors and hence the muscle mass increase in muscle fat leads to increase in the ceramide formation and increases the pro-inflammatory cytokines (TNF-α, IL-6) that may cause insulin resistance and decrease muscle mass. Fat metabolic dysregulation is also related to aging, T2D and obesity. Disturbances in glucose metabolism leads to decrease glucose utilization which leads to insulin resistance, that could in turn causes T2D and MS bone metabolism: the osteokines including, OPG, wnt-3a, sclerostin, FGF-23 affects muscle metabolism. The metabolites found as sarcopenic markers are pentadecanoic acid, 5′-MTA, MDA + 4HNE). In addition, the blood levels of myostatin and irisin can also indicate sarcopenic susceptibility. Dietary and lifestyle modifications can help counteract sarcopenia, with resistance exercise combined with leucine showing promise in stimulating myogenesis. BCAA, branched-chain amino acids; TNF-α, tumor necrosis factor alpha; IL-6, interleukin-6; T2D, type 2 diabetes; IR, insulin resistance; MS, metabolic syndrome; OPG, osteoprotegerin; FGF-23, fibroblast growth factor-23; 5′-MTA, 5′-methylthioadenosine; MDA, malondialdehyde; 4HNE, 4-hydroxynonenal.