Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin.
Department of Physical Therapy, Marquette University, Milwaukee, Wisconsin.
Am J Physiol Cell Physiol. 2020 Jun 1;318(6):C1238-C1251. doi: 10.1152/ajpcell.00575.2019. Epub 2020 Apr 29.
Age-induced declines in skeletal muscle contractile function have been attributed to multiple cellular factors, including lower peak force (P), decreased Ca sensitivity, and reduced shortening velocity (V). However, changes in these cellular properties with aging remain unresolved, especially in older women, and the effect of submaximal Ca on contractile function is unknown. Thus, we compared contractile properties of muscle fibers from 19 young (24 ± 3 yr; 8 women) and 21 older adults (77 ± 7 yr; 7 women) under maximal and submaximal Ca and assessed the abundance of three proteins thought to influence Ca sensitivity. Fast fiber cross-sectional area was ~44% larger in young (6,479 ± 2,487 µm) compared with older adults (4,503 ± 2,071 µm, < 0.001), which corresponded with a greater absolute P (young = 1.12 ± 0.43 mN; old = 0.79 ± 0.33 mN, < 0.001). There were no differences in fast fiber size-specific P, indicating the age-related decline in force was explained by differences in fiber size. Except for fast fiber size and absolute P, no age or sex differences were observed in Ca sensitivity, rate of force development (k), or V in either slow or fast fibers. Submaximal Ca depressed k and V, but the effects were not altered by age in either sex. Contrary to rodent studies, regulatory light chain (RLC) and myosin binding protein-C abundance and RLC phosphorylation were unaltered by age or sex. These data suggest the age-associated reductions in contractile function are primarily due to the atrophy of fast fibers and that caution is warranted when extending results from rodent studies to humans.
年龄导致的骨骼肌收缩功能下降归因于多种细胞因素,包括峰值力(P)降低、钙敏感性降低和缩短速度(V)降低。然而,这些细胞特性随年龄的变化仍未得到解决,尤其是在老年女性中,亚最大钙对收缩功能的影响尚不清楚。因此,我们比较了来自 19 名年轻(24±3 岁;8 名女性)和 21 名老年人(77±7 岁;7 名女性)肌肉纤维在最大和亚最大钙下的收缩特性,并评估了三种被认为影响钙敏感性的蛋白质的丰度。与老年人(4503±2071 µm,<0.001)相比,年轻人(6479±2487 µm)的快肌纤维横截面积大~44%,这与绝对 P 更大(年轻人=1.12±0.43 mN;老年人=0.79±0.33 mN,<0.001)相对应。快肌纤维大小特异性 P 没有差异,表明与年龄相关的力下降是由纤维大小差异解释的。除了快肌纤维大小和绝对 P,在慢肌或快肌中,钙敏感性、力发展速率(k)或 V 均未观察到年龄或性别差异。亚最大钙降低了 k 和 V,但在两性中,年龄均未改变这些作用。与啮齿动物研究相反,调节轻链(RLC)和肌球蛋白结合蛋白-C 的丰度和 RLC 磷酸化不受年龄或性别影响。这些数据表明,与年龄相关的收缩功能下降主要是由于快肌纤维萎缩所致,当将啮齿动物研究的结果推广到人类时应谨慎。