Epigenetic Drift of H3K27me3 in Aging Links Glycolysis to Healthy Longevity

We adapted ChIP-Rx method established in cells to fly tissues for quantitative ChIP-seq. We found the deposition of H3K27me3 during aging loses fidelity, resulting its propagation across the epigenome; lowering H3K27me3 by PRCs-deficiency promotes healthy lifespan by mitigating this trend. Quantitative multi-omic analysis converges on a central role of glycolysis, linking H3K27me3 dynamics to the regulation of glycolytic genes, which correspondingly rewire cellular metabolic homeostasis including energy and redox potential that impact lifespan and adult fitness. Compare H3K27me3 distribution with age and in two PRC2 trans-heterozygous double mutants. Compare transcriptome changes in normal aging and PRC2 mutants, 3 replicates for each genotype at given age.