Neuroprotection within the aging mammalian neuromuscular system

衰老哺乳动物神经肌肉系统内的神经保护

基本信息

批准号：
10404112
负责人：
GRAEME W DAVIS
金额：
$ 20.19万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-15 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10404112
关键词：
Ablation Address Adult Age Aging Anatomy Animal Model Biochemical Cognitive Data Degenerative Disorder Deterioration Disease Progression Drosophila genus Electrophysiology (science)Genetic Genetic Screening Health Health behavior Human Injury Integrins Laboratories Life Style Longevity Maintenance Modeling Molecular Motor Mus Muscle denervation procedure Muscular Atrophy Nervous system structure Neurodegenerative Disorders Neurologic Neuromuscular Junction Neurons Neurophysiology - biologic function Paper Physiological Process Publishing Quality of life Rodent Model Signal Transduction Synapses System Testing age effect age related aged aging population base combat diet and exercise frailty functional decline gene discovery healthspan high reward high risk mouse model muscle form neuromuscular neuromuscular function neuromuscular system neuroprotection normal aging novel novel therapeutic intervention preservation presynaptic protective effect resilience sarcopenia translational study

项目摘要

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.

抽象的在人类中，神经肌肉功能与年龄相关的下降与肌肉质量的丧失有关（肌肉减少症），健康和生活质量的脆弱和降解。唯一已知的治疗方法是基于生活方式的，包括运动和饮食。啮齿动物模型已用于证明与年龄有关神经肌肉连接（NMJ）的变化，包括碎片，重塑和最终肌肉的神经。我们最近证明了稳态可塑性的力量神经肌肉解剖学和功能，对有机健康，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。我们将其称为“稳态神经保护”。我们建议这种稳态神经保护在老年突触中也起作用，通常会抵消阴险与年龄有关的神经肌肉下降的影响。我们将确定稳态神经保护是否可以在啮齿动物模型中，可以加剧与年龄有关的肌肉减少症和与年龄有关的脆弱性，粘贴到新疗法人类的方法。