Elliott Jonathan E, Greising Sarah M, Mantilla Carlos B, Sieck Gary C
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA; Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA.
Respir Physiol Neurobiol. 2016 Jun;226:137-46. doi: 10.1016/j.resp.2015.10.001. Epub 2015 Oct 20.
The risk for respiratory complications and infections is substantially increased in old age, which may be due, in part, to sarcopenia (aging-related weakness and atrophy) of the diaphragm muscle (DIAm), reducing its force generating capacity and impairing the ability to perform expulsive non-ventilatory motor behaviors critical for airway clearance. The aging-related reduction in DIAm force generating capacity is due to selective atrophy of higher force generating type IIx and/or IIb muscle fibers, whereas lower force generating type I and IIa muscle fiber sizes are preserved. Fiber type specific DIAm atrophy is also seen following unilateral phrenic nerve denervation and in other neurodegenerative disorders. Accordingly, the effect of aging on DIAm function resembles that of neurodegeneration and suggests possible common mechanisms, such as the involvement of several neurotrophic factors in mediating DIAm sarcopenia. This review will focus on changes in two neurotrophic signaling pathways that represent potential mechanisms underlying the aging-related fiber type specific DIAm atrophy.
老年人发生呼吸系统并发症和感染的风险显著增加,这可能部分归因于膈肌的肌肉减少症(与衰老相关的肌无力和萎缩),降低了其产生力量的能力,并损害了执行对气道清理至关重要的呼气性非通气运动行为的能力。与衰老相关的膈肌产生力量能力的下降是由于高力量产生型IIx和/或IIb肌纤维的选择性萎缩,而低力量产生型I和IIa肌纤维的大小得以保留。单侧膈神经去神经支配后以及在其他神经退行性疾病中也可见到纤维类型特异性的膈肌萎缩。因此,衰老对膈肌功能的影响类似于神经退行性变,并提示可能存在共同机制,例如几种神经营养因子参与介导膈肌肌肉减少症。本综述将聚焦于两条神经营养信号通路的变化,这两条通路代表了与衰老相关的纤维类型特异性膈肌萎缩的潜在机制。