Epigenetic regulation of ageing: linking environmental inputs to genomic stability

Key Points Widespread epigenomic remodelling, at the level of DNA or histone protein modification, has been observed during ageing across species and cell types. Some epigenetic states can function as 'molecular clocks'. The experimental perturbation of chromatin modifiers can influence the lifespan of model organisms. Environmental inputs, such as diet, physical activity, hormones or pheromones, have been linked to remodelling of the epigenome as well as to changes in lifespan. Chromatin may thus act as a molecular integrator of environmental exposures. Random epigenetic changes, or epimutations, throughout life may trigger increases in transcriptional and genomic instability. The unique regulation of chromatin in germline cells might protect these cells more than somatic cells during ageing. Some ageing or age-related phenotypes, such as lifespan, fertility and stress resistance, may be inherited through successive generations in model organisms, through non-genetic mechanisms. The use of epigenetic drugs or epigenome-editing technologies may be a promising avenue for age-related therapeutics. The chromatin-based epigenetic changes that occur during ageing and the role of chromatin modifiers in lifespan have recently been highlighted. The importance of epigenome remodelling by environmental stimuli for transcriptional and genomic stability is emerging, and such remodelling could provide new targets to counter ageing or age-related diseases. Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodelling by environmental stimuli affects several aspects of transcription and genomic stability, with important consequences for longevity, and outline epigenetic differences between the 'mortal soma' and the 'immortal germ line'. Finally, we discuss the inheritance of characteristics of ageing and potential chromatin-based strategies to delay or reverse hallmarks of ageing or age-related diseases.