Genome-wide transcriptional stalling shapes the ageing transcriptome

Aging-related accumulation of biomolecular damage affects health- and lifespan, as shown by DNA repair deficient mouse models and human syndromes: continuous accumulation of persistent DNA damage leads to accelerated but fully bona fide aging and gene expression profiles alike normal aging.To understand how persistent DNA damage manifests (accelerated) aging and linked multimorbidity, we developed an in vivo nascent RNA (nRNA) sequencing method together with RNAPII ChIP-seq to monitor RNA biosynthesis in liver from aged (2yr) WT and progeroid (Xpg and Ercc1mutant) mice.