Peer-review started: July 29, 2014
First decision: August 14, 2014
Revised: August 27, 2014
Accepted: September 3, 2014
Article in press: September 4, 2014
Published online: September 28, 2014
Processing time: 87 Days and 10.9 Hours
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.
Core tip: Age itself is a major risk factor for the development of age-related cognitive decline, Alzheimer’s and cerebrovascular diseases. Increased life expectancy necessitates the need to understand the processes that underlie successful vs pathological brain ageing in order to develop early interventions which may assist in delaying if not reversing the detrimental effects of brain ageing. This review focuses on the signalling system of insulin and insulin-like growth factor-1 (IIS) and its roles in cerebral ageing; it highlights some conflicting literature opinions and incomplete understandings of the roles and mechanisms of the IIS system.