{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:03:17Z","timestamp":1790596997890,"version":"4.1.0"},"reference-count":0,"publisher":"Aging and Disease","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Dis"],"abstract":"<jats:p>Osteosarcopenia combines low bone strength with sarcopenia and increases the risks of falls, fractures, disability, and death. Recent reviews have catalogued extracellular vesicle (EV)-associated microRNAs in muscle-bone crosstalk, but intracellular microRNA function, EV association, experimentally administered EVs, and physiological tissue-to-tissue transfer are often discussed together. This focused narrative review applies an author-defined, non-validated four-tier framework to separate these inference levels using prespecified criteria for tissue-of-origin tracing, EV characterization, cargo perturbation, recipient validation, and in vivo phenotype. Within the studies reviewed, miR-125a-5p is the most complete preclinical muscle-to-bone candidate pathway, but its Tier-A assignment is provisional and supports causality only in the reported mouse models; it does not establish an exclusive single-cargo mechanism or human physiological transfer. Other muscle-cell EV microRNAs provide mechanistic but less complete evidence. No equivalent physiological bone-to-muscle EV-microRNA pathway meets Tier A; bone marrow stromal cell-derived EV miR-486-5p represents an experimentally administered therapeutic product rather than endogenous bone-to-muscle signaling. Most included studies concern related muscle or bone conditions or mechanistic models rather than directly defined osteosarcopenia. Human studies are small and heterogeneous, and none combines rigorous tissue-of-origin assignment, a prespecified osteosarcopenia phenotype, paired bone and muscle outcomes, and external validation. EV biomarkers and RNA\/EV therapies therefore remain investigational. This evidence-based asymmetry, rather than another catalogue of candidate microRNAs, distinguishes the present review and defines priorities for tissue-specific tracing, cargo-specific rescue, independent human validation, and prospective tests of clinical utility.<\/jats:p>","DOI":"10.14336\/ad.2026.1034","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:42:15Z","timestamp":1790595735000},"source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicle-Mediated microRNA Signaling in Osteosarcopenia: Emerging Insights into Age-Related Bone-Muscle Crosstalk"],"prefix":"10.14336","member":"5462","published-online":{"date-parts":[[2026]]},"container-title":["Aging and Disease"],"original-title":[],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:42:16Z","timestamp":1790595736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aginganddisease.org\/EN\/10.14336\/AD.2026.1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":0,"URL":"https:\/\/doi.org\/10.14336\/ad.2026.1034","relation":{},"ISSN":["2152-5250"],"issn-type":[{"value":"2152-5250","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]}}}