Circulating biomarkers associated with walking performance in elderly subjects: exploring miRNAs, metabolic and inflammatory biomarkers

Aging phenotype is characterized by musculoskeletal impairment that leads to diminished mobility and physical function. This study investigated whether circulating miRNAs and metabolic and inflammatory biomarkers may reflect the walking performance of the elderly. Elderly hospitalized for an acute condition and recruited from the ReportAge Biobank were grouped, based on their walking performance, in active subjects (n = 23, age: 83.0 ± 4.3), able to walk ≥ 1 km and who performed more than 1 h activity, and inactive subjects (n = 23, age: 85.0 ± 6.0), able to walk < 100 m and who performed < 1 h activity in the 3 days prior hospitalization. Plasma levels of 754 miRNAs were evaluated using OpenArray® platform, and miRNAs whose level was ± 2.5 fold (p < 0.05) were validated by qPCR. Target prediction for validated miRNAs was performed on MirWalk 3.0, Gene Ontology and pathway enrichment on Panther 19.0. Cytokines and metabolites associated with bone, muscle, and inflammation were evaluated from plasma samples using Luminex and ELISA. Among the 7 miRNAs found differentially expressed in active compared to inactive elderly after the initial screening, 4 miRNAs were validated: hsa-let7g-5p, hsa-miR-27a-3p, hsa-miR-361-5p, hsa-miR-574-3p, all upregulated in the active group. Gene Ontology and pathway enrichment analysis revealed the identified miRNAs potentially involved in muscle and bone metabolism during aging. Among cytokines, gp130 and IL-10 significantly differed between the two groups. This study suggests the potential association of specific circulating biomarkers with walking performance in elderly and their potential involvement in the molecular mechanism underlying age-associated musculoskeletal impairment.