Interrogating the Role of Epigenetic Signaling to PER2 in Healthful Adaptation to Calorie Restriction
Humans display a 24-hour periodicity in behavioral and molecular processes that deteriorates as they get older. Elderly individuals awaken earlier in the morning, sleep earlier at night, and have reduced molecular rhythms. While circadian abnormalities arise spontaneously during aging, similar syndromes are also observed throughout life in humans that harbor mutations in the circadian clock gene, PER2, and during feeding of the pro-longevity dietary intervention, calorie restriction. Understanding the mechanisms that link aging, calorie restriction, and the clock are essential for improving healthspan as genetic abrogation of the circadian clock in mice shortens lifespan and causes the development of age-associated morbidities. Dr. Levine’s research uses genetically modified mice that recapitulate behavioral and molecular abnormalities in circadian rhythms associated with aging and calorie restriction. His goal is to interrogate the mechanisms whereby the circadian clock senses calorie restriction to provide new therapeutic opportunities that improve healthspan.