雷帕霉素不会损害雌性小鼠运动诱导的肌肉适应。

IF 7.1 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Aging Cell Pub Date : 2025-07-24 DOI:10.1111/acel.70183
Christian J. Elliehausen, Szczepan S. Olszewski, Dennis M. Minton, Carolyn G. Shult, Aditya R. Ailiani, Michaela E. Trautman, Reji Babygirija, Dudley W. Lamming, Troy A. Hornberger, Adam R. Konopka
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引用次数: 0

摘要

越来越多的身体活跃的成年人正在服用mTOR抑制剂雷帕霉素,目的是延长健康寿命。然而,频繁服用雷帕霉素会破坏久坐状态下的代谢健康,并减弱对运动的合成代谢反应。在久坐不动的小鼠中,间歇性地每周给药一次雷帕霉素可使频繁使用雷帕霉素的许多负面代谢副作用降到最低。然而,不同的雷帕霉素给药计划如何影响代谢、身体和骨骼肌对自愿运动训练的适应尚不清楚。因此,我们验证了间歇性雷帕霉素(2 mg/kg;通过更频繁的给药计划(2mg /kg;3×/周)。动力提高了最大运动能力、绝对握力和肌纤维肥厚,在对照组和雷帕霉素组小鼠之间没有差异,尽管间歇性雷帕霉素组小鼠的自愿跑量更大。相反,与给药小鼠相比,频繁和间歇性使用雷帕霉素的小鼠在PoWeR后葡萄糖耐量和胰岛素敏感性受损;然而,与频繁使用雷帕霉素相比,间歇性雷帕霉素降低了对葡萄糖耐受不良的影响。总的来说,这些成年雌性小鼠的数据表明:(1)雷帕霉素在很大程度上与PoWeR对身体和骨骼肌的益处是一致的;(2)在自愿运动的情况下,雷帕霉素对葡萄糖代谢的有害影响可以通过间歇性给药来减少。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Rapamycin Does Not Compromise Exercise-Induced Muscular Adaptations in Female Mice

Rapamycin Does Not Compromise Exercise-Induced Muscular Adaptations in Female Mice

An increasing number of physically active adults are taking the mTOR inhibitor rapamycin off label with the goal of extending healthspan. However, frequent rapamycin dosing disrupts metabolic health during sedentary conditions and abates the anabolic response to exercise. Intermittent once-weekly 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 mg/kg; 1×/week) would avoid detrimental effects on adaptations to 8 weeks of progressive weighted wheel running (PoWeR) in adult female mice (5-month-old) by evading the sustained inhibitory effects on mTOR signaling by more frequent dosing schedules (2 mg/kg; 3×/week). PoWeR improved maximal exercise capacity, absolute grip strength, and myofiber hypertrophy with no differences between vehicle or rapamycin-treated mice despite greater voluntary running volume with intermittent rapamycin treatment. Conversely, frequent and intermittent rapamycin-treated mice had impaired glucose tolerance and insulin sensitivity compared to vehicle-treated 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.

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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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