Putting aging on pause: targeting SIRT6 and CDK9 to ameliorate age-related transcriptional dysregulation
Dr. Ibragimov investigates how age-related loss of RNA polymerase II promoter-proximal pausing undermines transcriptional fidelity. As pausing fades, two consequences emerge: inflammatory gene programs become dysregulated, and retrotransposons that should remain silent are reactivated, promoting genome instability and chronic inflammation. This project will combine epigenomic profiling and functional assays to quantify pausing and its consequences with age. Dr. Ibragimov will test whether clinically developed CDK9 inhibitors can restore pausing to re-suppress retrotransposons, stabilize immune gene regulation and increase lifespan in mice. By establishing pausing as a tractable regulatory node, his work aims to restore youthful gene regulation and delay age-related diseases.
