Aging is a universal biological phenomenon linked to many diseases, such as cancer or neurodegeneration. However, the molecular mechanisms underlying aging, or how lifestyle interventions such as cognitive stimulation can ameliorate this process, are yet to be clarified. Here, we performed a multi-omic profiling, including RNA-seq, ATAC-seq, ChIP-seq, EM-seq, SWATH-MS and single cell Multiome scRNA and scATAC-seq, in the dorsal hippocampus of young and old mouse subjects which were subject to cognitive stimulation using the paradigm of environmental enrichment. In this study we were able to describe the epigenomic landscape of aging and cognitive stimulation. This dataset contains information related to preprocessed datasets and additional files mentioned in the original manuscript.