Anatomical, neurochemical and functional properties of the mammalian brain change with age, and the trajectories of ageing are modified by many genetic and environmental risk factors, including lifestyle variables. Age‐related changes do not reflect a specific cellular program, but fundamental changes precipitating intracellular accumulation of reactive oxygen species and diminishing energy production may underlie age‐related deterioration of the brain structure and information processing properties. The latter has been hypothesised to bring about differential declines in cognitive functions that rely on processing of information of high novelty and low redundancy. These hypotheses are summarised in a Free‐Radical‐Induced Energetic and Neural Declines in Senescence (FRIENDS) model, some components of which have been demonstrated in longitudinal studies, while others can be inferred from cross‐sectional and postmortem investigations. The major obstacle to understanding brain ageing and its role in cognitive change remains the dearth of multi‐occasion longitudinal studies of the relevant constructs.
Key Concepts
Brain is a disproportional consumer of energy, which is necessary for maintaining its information processing machinery.
Energy crisis originating in mitochondrial dysfunction and causing further deterioration of the cellular machinery unfolds in time and thus promotes brain ageing.
Decline in metabolic, and vascular properties of the brain is precipitated by energy deficit and drives declines in multiple brain properties.
Brain shrinks with age, with key regions implicated in cognitive processing evidencing faster declines in comparison to sensory cortices.
Energy intensive functions, such as myelin maintenance and synaptogenesis, may be particularly vulnerable to ageing.
Age‐related declines are accelerated by genetic variants linked to vascular disease and inflammation as well as environmental pollution, stress and sedentary lifestyle.
Changes in iron homeostasis may precipitate structural brain changes.
When individual differences in age‐related cognitive changes are observed, they are coupled with alterations in brain structure and function.
Age‐related brain deterioration appears less pronounced in persons with high baseline cognitive performance.
Boosting cognitive performance and promoting active lifestyle as well as combatting pro‐inflammatory and metabolic risk factors may help to improve brain maintenance and mitigate age‐related declines.