Objective To investigate the regulatory effects of resistance exercise on Piezo1 in myoblasts within skeletal muscles of aged mice. Methods In animal experiments， thirty 20-month-old male C57BL/6 mice were randomly assigned to one of three groups： an aging control group， an aging exercise group， and an aging exercise inhibitor group. Additionally， ten 3-month-old young mice served as a young control group. The aging exercise group underwent 8 weeks of resistance exercise training， whereas the aging exercise inhibitor group received both 8 weeks of resistance exercise and intraperitoneal injections of GsMTx4. Exercise capacity was evaluated using grip strength tests and rotarod performance assays. Skeletal muscle cross-sectional area was assessed via hematoxylin-eosin staining， fibrosis was examined using Sirius red staining， and the proportion of p16-positive cells was determined by immunohistochemistry. In cellular experiments， senescence in myoblasts was induced with D-galactose （D-gal）， followed by activation of Piezo1 using Yoda1. The percentage of senescent cells was measured by SA-β-Gal staining， while protein expression levels of senescence markers （p16 and p21） and atrophy markers （Atrogin-1 and MuRF1） were quantified by Western blot analysis. Cell immunofluorescence staining was employed to assess the average fluorescence intensity of p21. Results （1）Compared with the aging control group， the aging + exercise group exhibited significant improvements in exercise capacity， quadriceps femoris mass index， skeletal muscle cross-sectional area， reduction in skeletal muscle fibrosis， and a lower p16-positive cell percentage （P < 0.05）； （2）These beneficial effects of exercise on aged skeletal muscle were attenuated following treatment with a Piezo1 inhibitor （P < 0.05）； （3）In vitro experiments demonstrated that activation of Piezo1 reduced the SA-β-Gal positive cell rate in myoblasts， downregulated the expression of senescence markers （p16 and p21） and atrophy-related markers （Atrogin-1 and MuRF1）， and decreased the average fluorescence intensity of p21 （P < 0.05）. Conclusion Resistance exercise suppresses myocyte aging through activation of Piezo1， thereby ameliorating age-related muscle atrophy in the elderly.