GEE Seminar - Professor Cleo Bishop, Queen Mary, University of London

Academic Host: Jürg Bahler
Abstarct: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we report a novel screening platform for the expedited discovery of compounds that restrain cellular ageing in vitro and enable extension of in vivo lifespan. For this, we developed a novel epigenetic clock, the CellAgeClock, to accurately monitor cellular ageing in adult human primary cells. We find that the CellAgeClock can detect decelerated passage-based cellular ageing of human primary cells treated with Rapamycin or Trametinib, well established longevity drugs. We then utilise the CellAgeClock as a screening tool for the identification of compounds which decelerate cellular ageing, uncovering novel anti-ageing drugs. We demonstrate that delayed cellular ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophilia. We show that the novel anti-ageing drugs increase longevity in vivo. In summary, our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.