Ageing is the greatest risk factor for virtually all degenerative diseases. Importantly, on a cellular level, ageing appears to be a largely epigenetic phenomenon that can be manipulated by pluripotency induction or transient expression of iPSC reprogramming factors. Although reprogramming can interconvert different cell types, what would be most exciting is to directly transform a given cell type from an “aged” to a “healthy young” state without a need for oncogenic pluripotency factors. Towards this goal we have developed & validated a network-based method to predict the TFs necessary for desired cellular transitions that we are integrating with chromatin state data to understand how ageing reshapes the cellular identity network. We have compelling data that youthful regenerative capacity and metabolism can be restored in aged mouse intestinal stem cells in vitro by directly correcting the age-altered transcriptional circuitry with appropriate TFs. To help build a foundation for reprogramming based rejuvenation strategies we are in the progress of creating a molecular atlas of 40 mouse and 4 human cell types to reveal the TFs (using RNAseq and ATACseq) that drive ageing in different cell types and lineages and whether there is conservation across species. In addition to bulk based approaches we are also profiling three somatic stem cell populations and their differentiation products via single RNAseq and single cell ATACseq to understand how homo- or heterogeneous the age-altered TF network is on a single cell level. Ultimately, we hope that our molecular atlas, once complete, will help build knowledge towards therapeutic control over the ageing process by advancing our understanding of cellular ageing.