Neuroprotection within the aging mammalian neuromuscular system

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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.