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However, frequent rapamycin dosing disrupts metabolic health during sedentary conditions and abates the anabolic response to exercise. Intermittent once\u2010weekly rapamycin dosing minimizes many negative metabolic side effects of frequent rapamycin in sedentary mice. However, it remains unknown how different rapamycin dosing schedules impact metabolic, physical, and skeletal muscle adaptations to voluntary exercise training. Therefore, we tested the hypothesis that intermittent rapamycin (2\u2009mg\/kg; 1\u00d7\/week) would avoid detrimental effects on adaptations to 8\u2009weeks of progressive weighted wheel running (PoWeR) in adult female mice (5\u2010month\u2010old) by evading the sustained inhibitory effects on mTOR signaling by more frequent dosing schedules (2\u2009mg\/kg; 3\u00d7\/week). PoWeR improved maximal exercise capacity, absolute grip strength, and myofiber hypertrophy with no differences between vehicle or rapamycin\u2010treated mice despite greater voluntary running volume with intermittent rapamycin treatment. Conversely, frequent and intermittent rapamycin\u2010treated mice had impaired glucose tolerance and insulin sensitivity compared to vehicle\u2010treated mice after PoWeR; however, intermittent rapamycin reduced the impact on glucose intolerance versus frequent rapamycin. Collectively, these data in adult female mice suggest that (1) rapamycin is largely compatible with the physical and skeletal muscle benefits of PoWeR and (2) the detrimental effects of rapamycin on glucose metabolism in the context of voluntary exercise may be reduced by intermittent dosing.<\/jats:p>","DOI":"10.1111\/acel.70183","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T09:15:14Z","timestamp":1753348514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Rapamycin Does Not Compromise Exercise\u2010Induced Muscular Adaptations in Female Mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Christian J.","family":"Elliehausen","sequence":"first","affiliation":[{"name":"Division of Geriatrics and Gerontology, Department of Medicine University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Geriatric Research Education and Clinical Center William S. 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