Decline in the function of the nervous system during ageing is a major cause both of loss of quality of life and of neurodegenerative disease in older people. We have recently shown that natural, age-related deterioration in neurotransmission can be rescued by reduced insulin/insulin-like growth factor signaling (IIS). Reduced IIS restores gap junctions (GJ) at neuromuscular synapses by increasing expression of endocytic recycling Rab GTPases, thereby promoting GJ formation. Elevated IIS, on the other hand, triggers degradation of GJ proteins into lysosomes. This project aims to identify the mechanism by which IIS dictates recycling or degradation of GJ proteins.
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