The changes in cognition that occur as humans age are thought to be a consequence of an array of age-related molecular changes in the brain, including alterations in the epigenetic mechanisms that regulate gene expression. However, it is only with recent advances in multi-omic and single-cell or single-nucleus sequencing that the molecular changes that affect specific neuron types have begun to be deciphered in detail. Chien et al. now add to this growing understanding by assessing the effects of ageing on the methylome and transcriptome of specific neuron types in the human cortex.

In this study, the authors profiled the DNA methylome and RNA transcriptome of more than 55,000 individual nuclei derived from the dorsolateral prefrontal cortex of 11 young adult and aged donors. Analysis of the resulting multi-omic dataset provided a number of insights into the effects of ageing on specific neuron types. For example, on the basis of the expression of canonical cell type markers, the authors reported a decline in the relative proportion of inhibitory neuron types — and in particular somatostatin (SST)- and vasoactive intestinal peptide (VIP)-expressing neurons — in the aged cortex.