Cerebral ageing is a complex biological process associated with progressing cerebrovascular disease and neuronal death.It does not always,however,associate with a functional decline,as the ageing mammalian brain retains considerable functional plasticity which supports successful cerebral ageing where age-related cognitive decline is modest.On the contrary,pathological cerebral ageing results in memory impairment and cognitive deterioration,with Alzheimer’s disease(AD)being a florid example.Trophic/growth factors promote brain plasticity;among them are peptides which belong to the insulin family.Preclinical research suggests that the evolutionarily conserved brain insulin/insulin-like growth factor-1(IGF-1)signalling system controls lifespan and protects against some features of AD such as neurodegeneration-related accumulation of toxic proteins and cognitive deficiencies,as observed in animal models.Insulin and IGF-1 activate cell signalling mechanisms which play protective and regenerative roles;abnormalities in the insulin/IGF-1 system may trigger a cascade of neurodegeneration in AD.AD patients show cerebral resistance to insulin which associates with IGF-I resistance and dysregulation of insulin/IGF-1 receptors as well as cognitive deterioration.This review is focused on the roles of the insulin/IGF-1 signalling system in cerebral ageing and its potential involvement in neurodegeneration in the human brain as seen against the background of preclinical evidence.