Department of Physical Therapy and Athletic Training, University of Utah, 520 Wakara Way, Salt Lake City, UT 84108, USA; George E. Wahlen Department of Veterans Affairs Medical Center, Geriatric Research, Education, and Clinical Center, 500 Foothill Dr., Salt Lake City, UT 84148, USA.
Department of Physical Therapy and Athletic Training, University of Utah, 520 Wakara Way, Salt Lake City, UT 84108, USA.
Exp Gerontol. 2022 Jun 15;163:111804. doi: 10.1016/j.exger.2022.111804. Epub 2022 Apr 9.
Metformin is the most commonly prescribed medication to treat diabetes. Emerging evidence suggests that metformin could have off target effects that might help promote healthy muscle aging, but these effects have not been thoroughly studied in glucose tolerant older individuals. The purpose of this study was to investigate the short-term effects of metformin consumption on skeletal muscle mitochondrial bioenergetics in healthy older adults.
We obtained muscle biopsy samples from 16 healthy older adults previously naïve to metformin and treated with metformin (METF; 3F, 5M), or placebo (CON; 3F, 5M), for two weeks using a randomized and blinded study design. Samples were analyzed using high-resolution respirometry, immunofluorescence, and immunoblotting to assess muscle mitochondrial bioenergetics, satellite cell (SC) content, and associated protein markers.
We found that metformin treatment did not alter maximal mitochondrial respiration rates in muscle compared to CON. In contrast, mitochondrial HO emission and production were elevated in muscle samples from METF versus CON (METF emission: 2.59 ± 0.72 SE Fold, P = 0.04; METF production: 2.29 ± 0.53 SE Fold, P = 0.02). Furthermore, the change in HO emission was positively correlated with the change in type 1 myofiber SC content and this was biased in METF participants (Pooled: R = 0.5816, P = 0.0006; METF: R = 0.674, P = 0.0125).
These findings suggest that acute exposure to metformin does not impact mitochondrial respiration in aged, glucose-tolerant muscle, but rather, influences mitochondrial-free radical and SC dynamics.
NCT03107884, clinicaltrials.gov.
二甲双胍是治疗糖尿病最常用的药物。新出现的证据表明，二甲双胍可能具有非靶向作用，有助于促进健康的肌肉衰老，但这些作用在葡萄糖耐量正常的老年人中尚未得到充分研究。本研究的目的是探讨短期服用二甲双胍对葡萄糖耐量正常的老年人骨骼肌线粒体生物能学的影响。
我们采用随机、双盲研究设计，从 16 名以前未使用过二甲双胍的健康老年人中获得肌肉活检样本，并用二甲双胍（METF；3F，5M）或安慰剂（CON；3F，5M）治疗两周。使用高分辨率呼吸测量法、免疫荧光和免疫印迹法分析样本，以评估肌肉线粒体生物能学、卫星细胞（SC）含量和相关蛋白标志物。
我们发现，与 CON 相比，二甲双胍治疗并未改变肌肉中的最大线粒体呼吸速率。相比之下，METF 与 CON 相比，肌肉样本中的线粒体 HO 发射和产生增加（METF 发射：2.59±0.72 SE 倍，P=0.04；METF 产生：2.29±0.53 SE 倍，P=0.02）。此外，HO 发射的变化与 1 型肌纤维 SC 含量的变化呈正相关，且这种相关性偏向于 METF 参与者（合并：R=0.5816，P=0.0006；METF：R=0.674，P=0.0125）。
这些发现表明，急性接触二甲双胍不会影响葡萄糖耐量正常的老年肌肉中的线粒体呼吸，但会影响线粒体自由基和 SC 动态。
NCT03107884，clinicaltrials.gov。
