Fogarty Matthew J, Brown Alyssa D, Sieck Gary C
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55902, USA.
Physiol Mini Rev. 2020 Jan-Feb;13(1):1-11.
Advanced age and amyotrophic lateral sclerosis (ALS) are both associated with a loss of motor neurons resulting in muscle fiber atrophy and muscle weakness. Aging associated muscle fiber atrophy and weakening is termed sarcopenia, but the association with motor neuron loss is not as clearly established as in ALS, probably related to the prolonged time course of aging-related changes. Although aging and ALS effects on limb muscle strength and neuromotor performance are serious, such effects on the diaphragm muscle can be life threatening. Converging evidence indicates that larger phrenic motor neurons, innervating more fatigable type IIx and/or IIb diaphragm muscle fibers (fast fatigue intermediate, FInt and fast fatigable, FF motor units) are more susceptible to degeneration with both aging and ALS compared to smaller phrenic motor neurons innervating type I and IIa diaphragm muscle fibers (slow and fast fatigue resistant motor units, respectively). The etiology of ALS and age-related loss of motor neurons appears to involve mitochondrial function and neuroinflammation, both chronic and acute exacerbation. How mitochondrial dysfunction, neuroinflammation and motor neuron size intersect is the focus of continuing investigation.
高龄和肌萎缩侧索硬化症（ALS）都与运动神经元的丧失有关，从而导致肌纤维萎缩和肌肉无力。与衰老相关的肌纤维萎缩和衰弱被称为肌肉减少症，但与运动神经元丧失的关联并不像在ALS中那样明确，这可能与衰老相关变化的时间进程较长有关。尽管衰老和ALS对肢体肌肉力量和神经运动表现的影响很严重，但对膈肌的影响可能会危及生命。越来越多的证据表明，支配更易疲劳的IIx型和/或IIb型膈肌纤维（快速疲劳中间型，FInt和快速疲劳型，FF运动单位）的较大膈运动神经元，与支配I型和IIa型膈肌纤维（分别为慢疲劳抵抗型和快疲劳抵抗型运动单位）的较小膈运动神经元相比，在衰老和ALS过程中更容易发生退化。ALS和与年龄相关的运动神经元丧失的病因似乎涉及线粒体功能和神经炎症，包括慢性和急性加重。线粒体功能障碍、神经炎症和运动神经元大小如何相互影响是持续研究的重点。
