Mosole Simone, Carraro Ugo, Kern Helmut, Loefler Stefan, Zampieri Sandra
Laboratory of Translation Myology, Department of Biomedical Sciences, University of Padova, Italy; Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Vienna, Austria.
IRCCS Fondazione Ospedale San Camillo , Venice, Italy.
Eur J Transl Myol. 2016 Nov 25;26(4):5972. doi: 10.4081/ejtm.2016.5972. eCollection 2016 Sep 15.
Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging.
ClinicalTrials.gov: NCT01679977.
组织化学、免疫组织化学、单根肌纤维凝胶电泳以及对衰老肌肉和神经的肌电图检查表明:i)去神经支配导致肌肉萎缩,ii)活动能力受损加速这一过程,iii)终生跑步可防止运动单位丧失。还将提及近期关于老年肌肉功能性电刺激(FES)对肌肉影响的确证结果,但我们将特别讨论终生增加的体力活动如何以及为何能维持肌纤维的再支配。通过分析共表达快肌球蛋白重链(MHC)和慢肌球蛋白重链的肌纤维的分布和密度,我们能够区分因活动相关可塑性而发生转变的肌纤维,以及那些使肌纤维特性适应去神经支配和再支配的肌纤维。在有终生高水平休闲活动史的七旬老人的肌肉活检中,与久坐不动的老年人相比,我们最近观察到:1. 小尺寸角形肌纤维(去神经支配的肌纤维)比例降低;2. 慢型纤维类型分组显著增加(再支配的肌纤维);3. 共表达快肌球蛋白重链和慢肌球蛋白重链的肌纤维稀疏存在。免疫组织化学特征从纤维类型调制和分组稀少的情况波动到几乎完全转变的肌肉,经历一个过程,即共表达快肌球蛋白重链和慢肌球蛋白重链的孤立纤维填补纤维分组之间的间隙。数据表明,终生高水平运动使身体能够适应与年龄相关的去神经支配的后果,并通过将原本会丢失的肌纤维招募到不同的慢运动单位来保存肌肉结构和功能。这与长期去神经支配或静止肌肉中所描述的情况相反。终生高水平活动的这些影响似乎主要作用于运动神经元,特别是那些一直更活跃的运动神经元,即慢运动神经元。数十年增加的活动后随之而来的优先再支配维持了神经元和肌纤维。所有这些结果为FES和电药物在老年肌肉年轻化中的应用开辟了有趣的前景,以延缓功能衰退和独立性丧失,这些是衰老晚期不可避免的负担。
ClinicalTrials.gov:NCT01679977。