Thomson David M, Gordon Scott E
Human Performance Laboratory, 363 Ward Sports Medicine Bldg., East Carolina Univ., Greenville, NC 27858, USA.
J Appl Physiol (1985). 2005 Feb;98(2):557-64. doi: 10.1152/japplphysiol.00811.2004. Epub 2004 Oct 1.
Skeletal muscle mass declines with age, as does the potential for overload-induced fast-twitch skeletal muscle hypertrophy. Because 5'-AMP-activated protein kinase (AMPK) activity is thought to inhibit skeletal muscle protein synthesis and may therefore modulate muscle mass and hypertrophy, the purpose of this investigation was to examine AMPK phosphorylation status (a marker of AMPK activity) and its potential association with the attenuated overload-induced hypertrophy observed in aged skeletal muscle. One-week overload of fast-twitch plantaris and slow-twitch soleus muscles was achieved in young adult (8 mo; n = 7) and old (30 mo; n = 7) Fischer344 x Brown Norway male rats via unilateral gastrocnemius ablation. Significant (P < or = 0.05) age-related atrophy (as measured by total protein content) was noted in plantaris and soleus control (sham-operated) muscles. In fast-twitch plantaris muscles, percent hypertrophy with overload was significantly attenuated with age, whereas AMPK phosphorylation status as determined by Western blotting [phospho-AMPK (Thr172)/total AMPK] was significantly elevated with age (regardless of loading status). There was also a main effect of loading on AMPK phosphorylation status in plantaris muscles (overload > control). Moreover, a strong and significant negative correlation (r = -0.82) was observed between AMPK phosphorylation status and percent hypertrophy in the overloaded plantaris muscles of all animals. In contrast to the plantaris, overload-induced hypertrophy of the slow-twitch soleus muscle was similar between ages, and AMPK phosphorylation in this muscle was also unaffected by age or overload. These data support the possibility that an age-related elevation in AMPK phosphorylation may partly contribute to the attenuated hypertrophic response observed with age in overloaded fast-twitch plantaris muscle.
骨骼肌质量会随着年龄增长而下降，超负荷诱导的快肌骨骼肌肥大的潜力也会下降。由于5'-AMP激活蛋白激酶（AMPK）的活性被认为会抑制骨骼肌蛋白质合成，因此可能调节肌肉质量和肥大，本研究的目的是检查AMPK磷酸化状态（AMPK活性的标志物）及其与衰老骨骼肌中观察到的超负荷诱导肥大减弱之间的潜在关联。通过单侧腓肠肌切除，在年轻成年（8个月；n = 7）和老年（30个月；n = 7）的Fischer344×Brown Norway雄性大鼠中实现了快肌比目鱼肌和慢肌比目鱼肌为期一周的超负荷。在比目鱼肌和比目鱼肌对照（假手术）肌肉中，观察到显著（P≤0.05）的与年龄相关的萎缩（通过总蛋白含量测量）。在快肌比目鱼肌中，随着年龄增长，超负荷引起的肥大百分比显著减弱，而通过蛋白质印迹法测定的AMPK磷酸化状态[磷酸化AMPK（Thr172）/总AMPK]则随着年龄显著升高（无论负荷状态如何）。负荷对比目鱼肌中AMPK磷酸化状态也有主要影响（超负荷>对照）。此外，在所有动物的超负荷比目鱼肌中，观察到AMPK磷酸化状态与肥大百分比之间存在强烈且显著的负相关（r = -0.82）。与比目鱼肌不同，慢肌比目鱼肌的超负荷诱导肥大在不同年龄之间相似，并且该肌肉中的AMPK磷酸化也不受年龄或超负荷的影响。这些数据支持了一种可能性，即与年龄相关的AMPK磷酸化升高可能部分导致了随着年龄增长在超负荷快肌比目鱼肌中观察到的肥大反应减弱。
