Epigenomics of aging in vertebrates

The functional decline of tissues is a hallmark of aging. A systematic study of genomic changes during aging has not been done, and may reveal important principles of genetic dysregulation with age. To understand how chromatin may impact tissue function during aging, we focused on chromatin marks linked to cell identity, broad H3K4me3 regions and clusters of H3K27ac. We collected samples throughout mouse lifespan to generate genomic maps, yielding 139 datasets. We identify age-related changes at the chromatin and transcription level, encompassing processes such as oxidative phosphorylation or interferon response. Interestingly the robust upregulation of interferon response correlates with increased transcription of endogenous retroviral sequences. Finally, pathways deregulated during mouse aging across tissues tend to be regulated similarly in other vertebrates, such as the African turquoise killifish. This study will help lay the groundwork to identify chromatin changes that could be leveraged to reactivate youthful functional states in aged cells.