Department of Molecular Physiology and Biophysics, University of Vermont, College of Medicine, Burlington, Vermont;
J Appl Physiol (1985). 2013 Oct 1;115(7):1004-14. doi: 10.1152/japplphysiol.00563.2013. Epub 2013 Jul 25.
We hypothesize that age-related skeletal muscle dysfunction and physical disability may be partially explained by alterations in the function of the myosin molecule. To test this hypothesis, skeletal muscle function at the whole muscle, single fiber, and molecular levels was measured in young (21-35 yr) and older (65-75 yr) male and female volunteers with similar physical activity levels. After adjusting for muscle size, older adults had similar knee extensor isometric torque values compared with young, but had lower isokinetic power, most notably in women. At the single-fiber and molecular levels, aging was associated with increased isometric tension, slowed myosin actin cross-bridge kinetics (longer myosin attachment times and reduced rates of myosin force production), greater myofilament lattice stiffness, and reduced phosphorylation of the fast myosin regulatory light chain; however, the age effect was driven primarily by women (i.e., age-by-sex interaction effects). In myosin heavy chain IIA fibers, single-fiber isometric tension and molecular level mechanical and kinetic indexes were correlated with whole muscle isokinetic power output. Collectively, considering that contractile dysfunction scales up through various anatomical levels, our results suggest a potential sex-specific molecular mechanism, reduced cross-bridge kinetics, contributes to the reduced physical capacity with aging in women. Thus these results support our hypothesis that age-related alterations in the myosin molecule contribute to skeletal muscle dysfunction and physical disability and indicate that this effect is stronger in women.
我们假设与年龄相关的骨骼肌功能障碍和身体残疾可能部分是由于肌球蛋白分子功能的改变引起的。为了验证这一假设，我们在身体活动水平相似的年轻（21-35 岁）和老年（65-75 岁）男性和女性志愿者中测量了整体肌肉、单纤维和分子水平的骨骼肌功能。在调整肌肉大小后，与年轻人相比，老年人的膝关节等长等张扭矩值相似，但等速功率较低，尤其是女性。在单纤维和分子水平上，衰老与等长张力增加、肌球蛋白肌动蛋白交联动力学减慢（肌球蛋白附着时间延长，肌球蛋白产生力的速率降低）、肌丝晶格硬度增加以及快速肌球蛋白调节轻链磷酸化减少有关；然而，这种年龄效应主要是由女性（即年龄与性别交互作用）驱动的。在肌球蛋白重链 IIA 纤维中，单纤维等长张力和分子水平的力学和动力学指标与整体肌肉等速功率输出相关。总的来说，考虑到收缩功能障碍通过各种解剖水平扩展，我们的结果表明，一种潜在的性别特异性分子机制，即交联动力学降低，可能导致女性随年龄增长而身体能力下降。因此，这些结果支持我们的假设，即肌球蛋白分子与年龄相关的改变导致骨骼肌功能障碍和身体残疾，并表明这种影响在女性中更强。
