Grant: Project Grant

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. This is such a well characterized phenomenon that we can now predict someone's biological age, vs. their chronological age, based on the state of their epigenome and even gauge their survival in late-life. Preliminary results from our group 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. To investigate this idea, we are proposing to collect 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.