Neuroprotection within the aging mammalian neuromuscular system

摘要 在人类中，与年龄相关的神经肌肉功能的下降与肌肉质量的丧失有关。 (骨质疏松症)，身体更加虚弱，健康和生活质量下降。唯一已知的治疗方法 是以生活方式为基础的，包括锻炼和节食。啮齿动物模型已经被用来证明与年龄有关的 神经肌肉接头(NMJ)的变化，包括碎裂、重塑和最终 肌肉失神经。我们最近已经证明了动态平衡可塑性的力量 神经肌肉解剖和功能，对生物健康、行为和寿命有显著影响 神经退行性疾病的啮齿动物模型。我们将其称为“动态平衡神经保护”。我们建议 这种动态平衡的神经保护在衰老的突触上也起作用，通常会抵消潜伏的 与年龄相关的神经肌肉衰退的影响。我们将确定动态平衡神经保护是否可以 增强了对抗啮齿动物模型中的石棺减少和年龄相关的虚弱，为新的治疗方法铺平了道路 在人类中的方法。

ABSTRACT In humans, the age-related decline in neuromuscular function is associated with loss of muscle mass (sarcopenia), increased frailty and a degradation of both health and quality of life. The only known treatments are life-style based, including exercise and diet. Rodent models have been used to demonstrate age-related changes at the neuromuscular junction (NMJ) including the fragmentation, remodeling and eventual denervation of muscle. We have recently demonstrated the power of homeostatic plasticity to preserve neuromuscular anatomy and function, with dramatic effects on organismal health, behavior and lifespan in rodent models of neurodegenerative disease. We refer to this as “Homeostatic Neuroprotection”. We propose that homeostatic neuroprotection also functions at the aged synapse, normally counteracting the insidious effects of age-related neuromuscular decline. We will determine whether homeostatic neuroprotection can be potentiated to combat sarcopenia and age-related frailty in rodent models, paving the way to new therapeutic approaches in human.