The role of epigenetics in cognitive ageing

Abstract

Objective: As the population is ageing, a better understanding of the underlying causes of age-related cognitive decline (cognitive ageing) is required. Epigenetic dysregulation is proposed as one of the underlying mechanisms for cognitive ageing. We review the current knowledge on epigenetics and cognitive ageing and appraise the potential of epigenetic preventative and therapeutic interventions.

Design: Articles on cognitive ageing and epigenetics in English were identified.

Results: Epigenetic dysregulation occurs with cognitive ageing, with changes in histone post-translational modifications, DNA methylation and non-coding RNA reported. However, human studies are lacking, with most being cross-sectional using peripheral blood samples. Pharmacological and lifestyle factors have the potential to change aberrant epigenetic profiles; but few studies have examined this in relation to cognitive ageing.

Conclusions: The relationship between epigenetic modifications and cognitive ageing is only beginning to be investigated. Epigenetic dysregulation appears to be an important feature in cognitive ageing, but whether it is an epiphenomenon or a causal factor remains to be elucidated. Clarification of the relationship between epigenetic profiles of different cell types is essential and would determine whether epigenetic marks of peripheral tissues can be used as a proxy for changes occurring in the brain. The use of lifestyle and pharmacological interventions to improve cognitive performance and quality of life of older adults needs more investigation.

Keywords: DNA methylation; RNA; ageing; cognitive ageing; epigenetics; gene expression; histones.