Normal ageing of the brain: Histological and biological aspects

All the hallmarks of ageing are observed in the brain, and its cells, especially neurons, are characterized by their remarkably long lifetime. Like any organ or system, the brain is exposed to ageing processes which affect molecules, cells, blood vessels, gross morphology and, uniquely for this organ, cognition. The preponderant cerebral structures are characterized by the cellular processes of neurons and glial cells and while the quantity of cerebral interstitial fluid is limited, it is now recognized as playing a crucial role in maintaining cerebral homeostasis. Most of our current knowledge of the ageing brain derives from studies of neurodegenerative disorders. It is interesting to note that common features of these disorders, like Tau, phosphoTau and amyloid peptide accumulation, can begin relatively early in life as a result of physiological ageing and are present in subclinical cases while also being used as early-stage markers of neurodegenerative diseases in progression. In this article, we review tissue and cellular modifications in the ageing brain. Commonly described macroscopic, microscopic and vascular changes that in the ageing brain are contrasted with those seen in neurodegenerative contexts. We also review the molecular changes that occur with age in the brain, such as modifications in gene expression, insulin/insulin-like growth factor 1 signalling dysfunction, post-translational protein modifications, mitochondrial dysfunction, autophagy and calcium conductance changes.