Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, Utah.
Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah.
Am J Physiol Cell Physiol. 2021 Apr 1;320(4):C566-C576. doi: 10.1152/ajpcell.00469.2020. Epub 2021 Jan 6.
Muscle progenitor cells (MPCs) in aged muscle exhibit impaired activation into proliferating myoblasts, thereby impairing fusion and changes in secreted factors. The antihyperglycemic drug metformin, currently studied as a candidate antiaging therapy, may have potential to promote function of aged MPCs. We evaluated the impact of 2 wk of metformin ingestion on primary myoblast function measured in vitro after being extracted from muscle biopsies of older adult participants. MPCs were isolated from muscle biopsies of community-dwelling older (4 male/4 female, ∼69 yr) adult participants before (pre) and after (post) the metformin ingestion period and studied in vitro. Cells were extracted from Young participants (4 male/4 female, ∼27 yr) to serve as a "youthful" comparator. MPCs from Old subjects had lower fusion index and myoblast-endothelial cell homing compared with Young, while Old MPCs, extracted after short-term metformin ingestion, performed better at both tasks. Transcriptomic analyses of Old MPCs (vs. Young) revealed decreased histone expression and increased myogenic pathway activity, yet this phenotype was partially restored by metformin. However, metformin ingestion exacerbated pathways related to inflammation signaling. Together, this study demonstrated that 2 wk of metformin ingestion induced persistent effects on Old MPCs that improved function in vitro and altered their transcriptional signature including histone and chromatin remodeling.
肌肉祖细胞（MPCs）在衰老肌肉中表现出增殖成肌母细胞的能力受损，从而损害融合和分泌因子的变化。抗高血糖药物二甲双胍目前作为一种候选抗衰老治疗药物进行研究，可能具有促进衰老 MPC 功能的潜力。我们评估了 2 周的二甲双胍摄入对从老年参与者的肌肉活检中提取的体外原代肌母细胞功能的影响。将 MPC 从社区居住的老年（4 名男性/4 名女性，约 69 岁）成年参与者的肌肉活检中分离出来，在二甲双胍摄入期之前（预）和之后（后）进行体外研究。从年轻参与者（4 名男性/4 名女性，约 27 岁）中提取细胞作为“年轻”的比较器。与年轻相比，老年受试者的 MPC 融合指数和肌母细胞-内皮细胞归巢率较低，而短期服用二甲双胍后提取的老年 MPC 在这两项任务中的表现都更好。对老年 MPC（与年轻相比）的转录组分析显示，组蛋白表达减少，肌肉生成途径活性增加，但二甲双胍部分恢复了这种表型。然而，二甲双胍摄入加剧了与炎症信号相关的途径。总之，这项研究表明，2 周的二甲双胍摄入对老年 MPC 产生了持久的影响，改善了体外功能，并改变了它们的转录特征，包括组蛋白和染色质重塑。
