BackgroundSarcopenia is thought to be underlined by age‐associated anabolic resistance and dysregulation of intracellular signalling pathways. However, it is unclear whether these phenomena are driven by ageing per se or other confounding factors.MethodsLean and healthy young (n = 10, 22 ± 3 years, BMI; 23.4 ± 0.8 kg/m2) and old men (n = 10, 70 ± 3 years, BMI; 22.7 ± 1.3 kg/m2) performed unilateral resistance exercise followed by intake of essential amino acids (EAA). Muscle biopsies were collected from the rested and the exercised leg before, immediately after and 60 and 180 min after EAA intake. Muscle samples were analysed for amino acid concentrations, muscle protein synthesis (MPS) and associated anabolic signalling.ResultsFollowing exercise, peak plasma levels of EAA and leucine were similar between groups, but the area under the curve was ~11% and ~28% lower in Young (p < 0.01). Absolute levels of muscle EAA and leucine peaked 60 min after exercise, with ~15 and ~21% higher concentrations in the exercising leg (p < 0.01) but with no difference between groups. MPS increased in both the resting (~0.035%·h−1 to 0.056%·h−1, p < 0.05) and exercising leg (~0.035%·h−1 to 0.083%·h−1, p < 0.05) with no difference between groups. Phosphorylation of S6K1Thr389 increased to a similar extent in the exercising leg in both groups but was 2.8‐fold higher in the resting leg of Old at the 60 min timepoint (p < 0.001). Phosphorylation of 4E‐BP1Ser65 increased following EAA intake and exercise, but differences between legs were statistically different only at 180 min (p < 0.001). However, phosphorylation of this site was on average 78% greater across all timepoints in Old (p < 0.01). Phosphorylation of eEF2Thr56 was reduced (~66% and 39%) in the exercising leg at both timepoints after EAA intake and exercise, with no group differences (p < 0.05). However, phosphorylation at this site was reduced by ~27% also in the resting leg at 60 min, an effect that was only seen in Old (p < 0.01). Total levels of Rheb (~45%), LAT1 (~31%) and Rag B (~31%) were higher in Old (p < 0.001).ConclusionLean and healthy old men do not manifest AR as evidenced by potent increases in MPS and mTORC1 signalling following EAA intake and exercise. Maintained anabolic sensitivity with age appears to be a function of a compensatory increase in basal levels of proteins involved in anabolic signalling. Therefore, our results suggest that age per se does not appear to cause AR in human skeletal muscle.

中文翻译：

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与年轻男性相比，健康、瘦弱的老年男性的合成代谢敏感性与氨基酸传感器和 mTORC1 激活剂的表达较高有关


背景肌肉减少症被认为与年龄相关的合成代谢耐药和细胞内信号通路失调。然而，目前尚不清楚这些现象是由衰老本身还是其他混杂因素驱动的。方法瘦而健康的年轻人 （n = 10， 22 ± 3 岁，BMI;23.4 ± 0.8 kg/m2）和老年人 （n = 10， 70 ± 3 岁，BMI;22.7 ± 1.3 kg/m2） 进行单侧阻力运动，然后摄入必需氨基酸 （EAA）。在 EAA 摄入前、摄入后、摄入后 60 和 180 min 收集休息和锻炼的腿部肌肉活检。分析肌肉样品的氨基酸浓度、肌肉蛋白质合成 （MPS） 和相关的合成代谢信号。结果运动后，两组之间 EAA 和亮氨酸的血浆峰值水平相似，但 Young 的曲线下面积降低 ~11% 和 ~28% （p < 0.01）。肌肉 EAA 和亮氨酸的绝对水平在运动后 60 分钟达到峰值，运动腿中的浓度分别高出 ~15% 和 ~21% （p < 0.01），但组间没有差异。静息组 （~0.035%·h-1 至 0.056%·h-1，p < 0.05） 和运动腿 （~0.035%·h-1 至 0.083%·h-1，p < 0.05） 的 MPS 均增加，组间无差异。S6K1Thr389 的磷酸化在两组的运动腿中增加到相似的程度，但在 60 分钟的时间点，Old 的静息腿的磷酸化高出 2.8 倍 （p < 0.001）。摄入 EAA 和运动后 4E-BP1Ser65 的磷酸化增加，但腿部之间的差异仅在 180 分钟时有统计学差异 （p < 0.001）。然而，在 Old 的所有时间点，该位点的磷酸化平均高出 78% （p < 0.01）。 在 EAA 摄入和运动后的两个时间点，运动腿中 eEF2Thr56 的磷酸化降低 （~66% 和 39%），没有组差异 （p < 0.05）。然而，在 60 分钟时，静息腿中该部位的磷酸化也减少了 ~27%，这种效果仅在 Old 中可见 （p < 0.01）。Rheb （~45%） 、 LAT1 （~31%） 和 Rag B （~31%） 的总水平在 Old 中较高 （p < 0.001）。结论瘦而健康的老年男性不会出现 AR，EAA 摄入和运动后 MPS 和 mTORC1 信号的强烈增加证明了这一点。随着年龄的增长而保持合成代谢敏感性似乎是参与合成代谢信号传导的蛋白质基础水平代偿性增加的函数。因此，我们的结果表明，年龄本身似乎不会导致人类骨骼肌的 AR。