Grant: Fellowship - Priority Announcement: Epigenetics

Understanding the biology of aging has never been more urgent for our society. According to the CIHR Institute of Aging, a 65 year-old person can expect to live roughly 20 more years. Despite medical improvements, the aging cohort is at highest risk for disease; 8% of seniors will develop Alzheimer's Disease and ~90% of all cancer diagnoses occur in those aged over 50 years.This declining health decreases individual quality of life and increases societal burden. Research into cellular processes of aging may suggest interventions to mitigate this decline. Cell function is a symphony of numerous molecular processes, which is disturbed dramatically by age. One important change affects how parts of genes are "stitched" (or spliced) together to create new proteins. In Hutchison-Gilford Progeria Syndrome (HGPS), rapid aging is caused by a DNA mutation that affects the stitching of a single gene. Remarkably, this very defect also gradually occurs in normal aging cells. Several studies have noted widespread changes in gene stitching with age, but the causes of this phenomenon are poorly understood. I propose to identify which genes show changes in stitching in aging human post-mortem brain and - importantly - to try to uncover its molecular causes. My hypothesis is that chemical "flags", or epigenetic marks, on these genes are responsible for changing their stitching. These marks influence gene function in several ways, including how a gene is stitched. Epigenetic marks change with age for unknown reasons. This research may find other genes that, like the HGPS gene, contribute distinct properties to aging cells. Seeing the overall picture of such changes could suggest structural or functional triggers for this alteration in gene stitching. In the long run, this research could help identify to what extent the process of gene stitching could be used to decelerate aging.