Serum-derived extracellular vesicles as biological indicator of mobility resilience in older adults

The decline in mobility with aging is a major health concern, associated with a high risk for disability. Despite the widespread prevalence of gait slowing in elderly adults, this issue has not been adequately addressed. The central nervous system and skeletal muscle system are key regulators of gait speed. However, direct molecular communication along the brain-muscle axis and the role of these interactions in mobility resilience remain poorly studied. Recently, extracellular vesicles (EV), membrane bound vesicles secreted by cells, have emerged as a key player in long distance inter-cellular communication. Nevertheless, the potential of EVs as biological predictor of mobility resilience in older adults has not been yet studied. In the present study, we used serum samples from 23 participants with gait speed >1.0 m/sec (mobility-resilient group) and 22 participants with gait <1.0 m/sec (mobility non-resilient group) from the Health, Aging and Body Composition (Health ABC) study. First, total circulating serum EVs were isolated and characterized for small noncoding RNAs using un-biased small noncoding RNA sequencing. Given the central role of mitochondria in muscle energy metabolism and their emerging link to age-related physical decline, next, muscle-derived EVs (MDE) were isolated and characterized for specific mitochondrial markers (TOM20, mtCox2, PDH, and VDAC) by flow cytometry, the expression of a panel of 13 miRNAs related to mitochondrial function by RT-PCR, and PPAR-{gamma} expression by ELISA. The results showed differential enrichment of various miRNAs, circRNAs, and mitochondrial proteins in total EVs and/or MDE between mobility-resilient and non-resilient groups, highlighting their potential as non-invasive biomarkers for mobility outcomes. Overall, the findings from the present study suggest a role for serum EVs in mediating molecular communication related to functional aging phenotypes and underscores the potential of EV biomarkers in modulating mobility and promoting healthy aging.