Specific Profiles Of Circulating Mediators Characterize Older Persons With Physical Frailty And Sarcopenia

Chronic inflammation, changes in body composition, muscle loss (sarcopenia) and decreasing homeostatic reserve (frailty) are hallmarks of aging. Several circulating inflammatory markers have been associated with these age-related conditions. However, a gold standard biomarker able to predict functional impairment in older adults is currently unavailable. Muscle is crucial for several metabolic processes, including protein/aminoacid metabolism. Perturbations in protein/aminoacid metabolism may play also a role in the development of physical frailty and sarcopenia (PF&S). The simultaneous analysis of an array of circulating aminoacid/metabolites and their relationship with inflammatory mediators may help gain insights in the pathophysiology of PF&S. To this aim, we analyzed the profile of circulating inflammatory mediators and amino acids in older people with and without PF&S. More than five hundred persons aged 70+ years were screened. Of these, sixty (20 men and 40 women; mean age 76.9±4.8 years) were diagnosed with PF&S. Thirty (14 men and 16 women) non-sarcopenic, non-frail persons were enrolled in the control group. A panel of 27 cytokines, chemokines and growth factors was analyzed via a multiplex, magnetic bead-based immunoassay on a Bio-Plex® System with Luminex xMap Technology. A panel of 37 serum amino acids and derivatives was assessed by UPLC-MS. Multi-block partial least squares discriminant analysis (PLS-DA) was employed to explore the relationship among inflammatory and amino acid profiles of people with PF&S. Double cross-validation procedures were used to validate the predictive ability of the PLS-DA model. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 85.5 ± 4.4 for persons with PF&S and 88.3 ± 3.6 for controls. As for the amino acid profile, people with PF&S showed higher levels of aspartic acid, asparagine, taurine, citrulline, alpha-aminobutyric acid, methionine, and glutamic acid. Increased levels of interleukin-8, myeloperoxidase, and platelet derived growth factor-BB were also found in people with PF&S. The dissection of these patterns may provide novel insights into the role played by inflammatory mediators and protein/amino acid perturbations in the disabling cascade associated with PF&S and possible new targets for interventions.