Faraldi Martina, Provinciali Mauro, Di Rosa Mirko, Moresi Raffaella, Sansoni Veronica, Gomarasca Marta, Gerosa Laura, Malvandi Amir Mohammad, Lattanzio Fabrizia, Banfi Giuseppe, Lombardi Giovanni
Laboratory of Experimental Biochemistry & Advanced Diagnostics, IRCCS Ospedale Galeazzi-Sant'Ambrogio, Via Cristina Belgioioso 173, 20157, Milan, Italy.
Advanced Technology Center for Aging Research, IRCCS INRCA, 60121, Ancona, Italy.
Geroscience. 2025 Jan 20. doi: 10.1007/s11357-025-01510-2.
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.
衰老表型的特征是肌肉骨骼功能受损，导致活动能力和身体功能下降。本研究调查了循环miRNA以及代谢和炎症生物标志物是否能反映老年人的步行能力。从ReportAge生物样本库招募的因急性疾病住院的老年人，根据其步行能力分为活跃组（n = 23，年龄：83.0 ± 4.3岁），能够行走≥1公里且活动时间超过1小时；以及不活跃组（n = 23，年龄：85.0 ± 6.0岁），能够行走<100米且在住院前3天内活动时间<1小时。使用OpenArray®平台评估754种miRNA的血浆水平，水平变化±2.5倍（p < 0.05）的miRNA通过qPCR进行验证。对验证后的miRNA进行靶标预测，在MirWalk 3.0上进行，基因本体论和通路富集分析在Panther 19.0上进行。使用Luminex和ELISA从血浆样本中评估与骨骼、肌肉和炎症相关的细胞因子和代谢物。在初步筛选后发现，与不活跃老年人相比，活跃老年人中有7种miRNA差异表达，其中4种miRNA得到验证：hsa-let7g-5p、hsa-miR-27a-3p、hsa-miR-361-5p、hsa-miR-574-3p，均在活跃组中上调。基因本体论和通路富集分析表明，所鉴定的miRNA可能参与衰老过程中的肌肉和骨骼代谢。在细胞因子中，两组之间gp130和IL-10存在显著差异。本研究表明特定循环生物标志物与老年人步行能力之间可能存在关联，以及它们可能参与与年龄相关的肌肉骨骼损伤的分子机制。
