February 20


Biodesign Auditorium
727 E. Tyler St. Tempe
AZ 85287

The epigenome is reset during embryogenesis and matures around the end of development. Large scale genomic studies have now shown considerable proliferation dependent epigenome changes (drift) in aging cells (DNA methylation instability, chromatin instability). Comparison of rodent, primate and human aging shows that DNA methylation drift is conserved, depends primarily on chronologic age, and can be predicted to a certain degree by local genomic features (e.g. retrotransposons). It can therefore be argued that this epigenomic instability is a necessary result of the evolution of complex genomes that lack reprogramming capabilities in adult cells. Epigenetic drift creates gene expression variation in aging tissues that serve as an enabler of Darwinian evolution at the tissue level. Selective pressures result in cells with unique epigenetic programs that lead to diseases such as cancer or atherosclerosis. Importantly, epigenetic drift can be modulated by exposures (inflammation and perhaps diet), providing a mechanistic link between lifestyle and disease. In turn, epigenetic reprogramming could be useful for prevention and treatment of age-related pathology. In leukemias, reprogramming by DNA methylation inhibitors has gained acceptance as effective therapy for myeloid leukemias, and drugs for other epigenetic targets are rapidly proceeding towards clinical trials.