Buck Institute for Research on Aging

Forkhead Regulates Circadian Clocks Upon Dietary Restriction

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In today’s fast-paced environment, we humans work hard and long in a day’s time. Work hours have increased significantly, and we start the day before the sun comes out and stay awake hours after the normal sunlight has faded. By doing all this, we constantly keep our circadian clock system under stress. As clocks are key regulators of metabolism, one negative outcome could be that with time (age) the stress on clocks will result in misregulation of metabolism resulting in age-related cellular metabolic dysfunctions leading to increased diabetes, neurodegenerative diseases and obesity. While keeping ourselves working over the day, we also try to maintain a healthy and active lifestyle by doing exercise and eating a well-balanced diet. One such condition, dietary restriction, has been shown to improve health in most of the species tested, including fruit flies (Drosophila melanogaster), mice and human. Over the last three years, I have shown that circadian clock machinery is required for the positive effects (increased lifespan, starvation and fat turnover) of dietary restriction (Katewa et al. Cell metabolism, 2016). I have also identified a key role of medium chain triglycerides (MCT) in dietary restriction. This MCT’s, that are synthesized and cycling in a clock dependent manner under dietary restriction conditions could be very important. The idea is to use their analogs, may be as dietary supplements to improve the circadian rhythms, improve sleep patterns and slow aging and age-related metabolic disorders in the older human population.