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下降与肌肉质量的损失有关 （肌肉减少症）、增加的虚弱以及健康和生活质量的下降。唯一已知的治疗方法 是基于生活方式的，包括锻炼和饮食。啮齿动物模型已被用于证明年龄相关的 神经肌肉接头（NMJ）的变化，包括断裂、重塑和最终的 肌肉去神经支配。我们最近已经证明了内稳态可塑性的力量， 神经肌肉解剖和功能，对生物体健康，行为和寿命产生巨大影响， 神经退行性疾病的啮齿动物模型。我们称之为"稳态神经保护"。我们提出 稳态神经保护作用也在老化的突触中发挥作用，通常会抵消潜在的神经保护作用。 与年龄相关的神经肌肉衰退的影响。我们将确定稳态神经保护是否可以 在啮齿类动物模型中增强对抗肌肉减少症和年龄相关的虚弱，为新的治疗方法铺平了道路 接近人类。

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.