Project Overview

One of the most important questions of biomedical research is “why do we ail as we age?”. This may be in part due to a breakdown of the body’s circadian rhythm – the physiological process that tunes up or down various bodily functions during the 24 hr cycle. Another aspect of our biology that changes in response to the aging process is the epigenome. This is an additional layer of information attached to DNA that regulates and directs how and when genes should be expressed, or transcribed, in each cell. This layer of information is not copied as accurately as DNA and is susceptible to environmental factors, which causes it to change gradually as people age. Preliminary results from Dr. Petronis and his team show that the underlying molecular infrastructure of our circadian rhythm is in part directed by changes in the epigenome. Given the concurrent deterioration of the epigenome and circadian rhythm during the aging process, it seems conceivable that well characterized alterations to the epigenome during the aging process are disrupting our circadian physiology and likely playing a significant role in our declining health in old age. For this project, the team is collecting brains from mice of 5 different ages, from adolescence to old age, over the course of 24 hours in each separate group to: 1) fully catalogue all the transcriptional and epigenetic components of the circadian rhythm, in different parts of the brain, 2) identify the ones that are affected by age, 3) analyze how these may be related to aging brain diseases, so that this effort can contribute towards a remedy.

Principal Investigator

Art Petronis , University of Toronto/CAMH

Team Members

Jose Nobrega, Centre for Addiction and Mental Health

Albert Wong, Centre for Addiction and Mental Health

Martin Ralph, University of Toronto

Partners and Donors

Centre for Addiction and Mental Health