Abstract：
The rationale for the use of metformin as a treatment to slow aging was largely based on data collected from metabolically unhealthy individuals. For healthspan extension metformin will also be used in periods of good health. To understand the potential context specificity of metformin treatment on skeletal muscle, we used a rat model (high-capacity runner/low-capacity runner [HCR/LCR]) with a divide in intrinsic aerobic capacity. Outcomes of metformin treatment differed based on baseline intrinsic mitochondrial function, oxidative capacity of the muscle (gastroc vs soleus), and the mitochondrial population (intermyofibrillar vs. subsarcolemmal). Metformin caused lower ADP-stimulated respiration in LCRs, with less of a change in HCRs. However, a washout of metformin resulted in an unexpected doubling of respiratory capacity in HCRs. These improvements in respiratory capacity were accompanied by mitochondrial remodeling that included increases in protein synthesis and changes in morphology. Our findings raise questions about whether the positive findings of metformin treatment are broadly applicable.
摘要：
使用二甲双胍作为治疗延缓衰老的理由主要基于从代谢不健康个体收集的数据。对于健康扩展，二甲双胍也将用于健康时期。了解二甲双胍治疗骨骼肌的潜在背景特异性，我们使用了大鼠模型(高容量跑步者/低容量跑步者[HCR/LCR]),其固有有氧能力存在差异.二甲双胍治疗的结果基于基线内在线粒体功能而有所不同，肌肉的氧化能力（胃与比目鱼肌），和线粒体群体(肌原纤维与肌膜下）。二甲双胍导致LCR中ADP刺激的呼吸降低，HCR的变化较小。然而,二甲双胍的洗脱导致HCRs的呼吸容量意外增加了一倍.呼吸能力的这些改善伴随着线粒体重塑，包括蛋白质合成的增加和形态的变化。我们的发现提出了关于二甲双胍治疗的阳性发现是否广泛适用的问题。
