肌发生
内科学
内分泌学
骨骼肌
C2C12型
体内
体外
心肌细胞
离体
蛋白激酶B
亮氨酸
生物
磷酸化
化学
医学
氨基酸
细胞生物学
生物化学
生物技术
作者
Steve Allen,Ryan N. Marshall,S. Edwards,Janet M. Lord,Gareth G. Lavery,Leigh Breen
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:2021-07-01
卷期号:321 (1): C26-C37
被引量:11
标识
DOI:10.1152/ajpcell.00093.2021
摘要
In vitro models of muscle aging are useful for understanding mechanisms of age-related muscle loss and aiding the development of targeted therapies. To investigate mechanisms of age-related muscle loss in vitro utilizing ex vivo human serum, fasted blood samples were obtained from four old (72 ± 1 yr) and four young (26 ± 3 yr) men. Older individuals had elevated levels of plasma CRP, IL-6, HOMA-IR, and lower concentric peak torque and work-per-repetition compared with young participants ( P < 0.05). C2C12 myotubes were serum and amino acid starved for 1 h and conditioned with human serum (10%) for 4 h or 24 h. After 4 h, C2C12 cells were treated with 5 mM leucine for 30 min. Muscle protein synthesis (MPS) was determined through the surface sensing of translation (SUnSET) technique and regulatory signaling pathways were measured via Western blot. Myotube diameter was significantly reduced in myotubes treated with serum from old, in comparison to young donors (84%, P < 0.001). MPS was reduced in myotubes treated with old donor serum, compared with young serum before leucine treatment (32%, P < 0.01). MPS and the phosphorylation of Akt, p70S6K, and eEF2 were increased in myotubes treated with young serum in response to leucine treatment, with a blunted response identified in cells treated with old serum ( P < 0.05). Muscle protein breakdown signaling pathways did not differ between groups. In summary, we show that myotubes conditioned with serum from older individuals had decreased myotube diameter and MPS compared with younger individuals, potentially driven by low-grade systemic inflammation.
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