Serum metabolomics reveals shared biomarkers and potential common mechanisms of sarcopenia and cognitive impairment

Both sarcopenia (Sp) and cognitive impairment (CI) are common geriatric syndromes that interact with and influence the other. However, the exact mechanism underlying the interaction between these syndromes is still unclear and needs to be further explored. The objectives of this study were to investigate blood metabolomic findings in patients with Sp and/or CI, analyze possible biomarkers and potential crossover mechanisms, and discuss the clinical implications of these mechanisms. By using a targeted metabolomic approach, we analyzed serum from 50 patients with Sp, 50 patients with CI, 20 patients with both Sp and CI, and 40 healthy individuals. Metabolomic studies in Sp patients revealed that key metabolites of amino acid metabolism, protein digestion and absorption, amino acid biosynthesis, and neurological pathways are associated with Sp. Tyrosine, 2-phenylacetamide, 5′-deoxyadenosine, leucine and phenylalanyl isoleucine were the top five differentially abundant metabolites. Metabolomic studies related to CI revealed that important metabolites of amino acid biosynthesis, amino acid metabolism, signal transduction, and neurological pathways are strongly associated with CI. Sphingolipid (SM 42:1;2), 2-phenylacetamide, tyrosine, 5′-deoxyadenosine, and flavonoid levels were significantly different in patients with CI. In addition to neurological pathways, the shared metabolomic profiles suggested that mitochondrial dysfunction might play a key role in Sp and CI. Among these profiles, tyrosine, 2-phenylacetamide, and 5′-deoxyadenosine were common differentially abundant metabolites in Sp and CI and might be common biomarkers for both. These results were validated through serum metabolomic analysis of patients with both Sp and CI. These metabolomic studies of Sp and CI provided new perspectives for understanding the relationship between these syndromes. Disturbed energy metabolism due to mitochondrial dysfunction might regulate the pathological mechanisms common to Sp and CI. This improved understanding could provide a more effective strategy for health management in elderly individuals.