Cellular reprogramming and ageing

Until recently the process of how genes change activity from birth to adulthood and into old age was largely unknown. The Nefzger lab has mapped chromatin and transcriptional changes across >45 mouse and human cell types and uncovered a conserved mechanism that links organismal maturation with ageing (Cell Metabolism,2024). We identified the transcription factor AP-1 as a key driver of this shared trajectory. During maturation, AP-1 activates adult gene programs (in concert with hormonal cues) while diverting cell-identity TFs away from developmental regulatory elements as growth slows and tissues mature. Beyond early adulthood, stress- and inflammation-induced AP-1 activity continues to open chromatin actively shutting down “youthful” gene programs by hijacking this developmental mechanism. Our work thus reframes ageing not as a random drift but as a predictable TF-network remodelling process, in which escalating AP-1 activity progressively reconfigures cell identity to drive decline. These findings set the stage for new interventions that act on the epigenome to preserve function and extend healthy life.