Choi Seung Jun, Lim Jae-Young, Nibaldi Eva G, Phillips Edward M, Frontera Walter R, Fielding Roger A, Widrick Jeffrey J
Krivickas Muscle Cell Physiology Laboratory, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School, 125 Nashua Street, Boston, MA 02114, USA.
Age (Dordr). 2012 Feb;34(1):215-26. doi: 10.1007/s11357-011-9228-2. Epub 2011 Mar 24.
Muscles of old laboratory rodents experience exaggerated force losses after eccentric contractile activity. We extended this line of inquiry to humans and investigated the influence of fiber myosin heavy chain (MHC) isoform content on the injury process. Skinned muscle fiber segments, prepared from vastus lateralis biopsies of elderly men and women (78 ± 2 years, N = 8), were subjected to a standardized eccentric contraction (strain, 0.25 fiber length; velocity, 0.50 unloaded shortening velocity). Injury was assessed by evaluating pre- and post-eccentric peak Ca(2+)-activated force per fiber cross-sectional area (F (max)). Over 90% of the variability in post-eccentric F (max) could be explained by a multiple linear regression model consisting of an MHC-independent slope, where injury was directly related to pre-eccentric F (max), and MHC-dependent y-intercepts, where the susceptibility to injury could be described as type IIa/IIx fibers > type IIa fibers > type I fibers. We previously reported that fiber type susceptibility to the same standardized eccentric protocol was type IIa/IIx > type IIa = type I for vastus lateralis fibers of 25-year-old adults (Choi and Widrick, Am J Physiol Cell Physiol 299:C1409-C1417, 2010). Modeling combined data sets revealed significant age by fiber type interactions, with post-eccentric F (max) deficits greater for type IIa and type IIa/IIx fibers from elderly vs. young subjects at constant pre-eccentric F (max). We conclude that the resistance of the myofilament lattice to mechanical strain has deteriorated for type IIa and type IIa/IIx, but not for type I, vastus lateralis fibers of elderly adults.
老年实验啮齿动物的肌肉在离心收缩活动后会经历过度的力量损失。我们将这一研究方向扩展到人类,并研究了纤维肌球蛋白重链(MHC)同工型含量对损伤过程的影响。从老年男性和女性(78±2岁,N = 8)的股外侧肌活检样本中制备的去皮肤肌纤维段,进行标准化的离心收缩(应变,0.25纤维长度;速度,0.50无负荷缩短速度)。通过评估离心收缩前后每纤维横截面积的峰值钙(Ca2+)激活力(F(max))来评估损伤情况。离心收缩后F(max)超过90%的变异性可以由一个多元线性回归模型来解释,该模型包括一个与MHC无关的斜率,其中损伤与离心收缩前的F(max)直接相关,以及与MHC相关的y轴截距,其中损伤易感性可描述为IIa/IIx型纤维>IIa型纤维>I型纤维。我们之前报道过,对于25岁成年人的股外侧肌纤维,相同标准化离心方案下的纤维类型易感性为IIa/IIx型>IIa型 = I型(Choi和Widrick,《美国生理学杂志:细胞生理学》299:C1409 - C1417,2010)。对合并数据集进行建模显示出显著的年龄与纤维类型相互作用,在离心收缩前F(max)恒定的情况下,老年受试者的IIa型和IIa/IIx型纤维离心收缩后F(max)的 deficit 比年轻受试者更大。我们得出结论,对于老年成年人的股外侧肌纤维,IIa型和IIa/IIx型纤维的肌丝晶格对机械应变的抵抗力已经下降,但I型纤维没有。