Piezo1 Mechanotransduction in Skeletal Muscle: Convergence with Noncoding RNA Regulation in Myogenesis, Regeneration, and Sarcopenia

Skeletal muscle is a continuously load-bearing tissue whose growth, repair, and age-related decline are governed by mechanical signals, and failure of this mechano-regulation underlies disuse atrophy and sarcopenia. Piezo1, a mechanically activated cation channel, has emerged as a tractable transducer of these signals in muscle, contributing to satellite-cell quiescence and senescence, regenerative division, myoblast fusion, and the response to loading and unloading. In parallel, the myogenic noncoding RNA program is among the best defined in any lineage, with the myomiRs miR-1/133/206, the long noncoding RNA LINC-MD1, and the circular RNA circ-ZNF609 as established regulators of the proliferation-to-differentiation transition. These layers are linked because Piezo1-evoked calcium influx feeds the RhoA/ROCK-actin-MRTFA-SRF and YAP/TAZ axis that drives myogenic transcription, yet no direct coupling between Piezo1 and noncoding RNAs has been demonstrated in skeletal myocytes. Drawing on validated precedents from vascular, cardiac, and tendon tissues, this review consolidates the two pillars, frames their convergence as a testable question, distinguishes validated relationships from hypotheses, and proposes three falsifiable predictions using an unbiased candidate-selection strategy. The contribution of this review is this testable framework rather than any specific candidate list. Mechanically tunable noncoding RNAs may thus represent an underexplored node for counteracting disuse atrophy and sarcopenia.