Serum-Derived Extracellular Vesicles as Biological Indicator of Mobility Resilience in Older Adults

Mobility decline with aging is a major health concern, associated with a higher risk for disability. Despite the prevalence of gait slowing in elderly adults, this issue has not been adequately addressed. The central nervous and skeletal muscle systems are key regulators of gait speed. However, direct molecular communication along the brain-muscle axis and their interactions in mobility resilience remain poorly studied. Extracellular vesicles (EVs) have emerged as a key player in long-distance inter-cellular communication. Nevertheless, the potential of EVs as biological predictors of mobility resilience in older adults has not been studied. We used serum from 23 participants with gait speed > 1.0 m/s (resilient) and 22 participants with gait < 1.0 m/s (non-resilient) from the Health, Aging and Body Composition (Health ABC) study. Total circulating serum EVs were isolated and small noncoding RNAs characterized using un-biased sequencing. Given the central role of mitochondria in muscle energy metabolism and link to age-related physical decline, next, muscle-derived EVs (MDE) were isolated and characterized for mitochondrial markers (TOM20, mtCox2, PDH, and VDAC) by flow cytometry, 13 miRNAs related to mitochondrial function by RT-PCR, and PPAR-γ 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, these findings suggest a role for serum EVs in mediating molecular communication related to functional aging phenotypes and underscore the potential of EV biomarkers in modulating mobility and promoting healthy aging.