PROLONGED DAILY FASTING TIMES ARE BEST WHEN COMBINED WITH CALORIE RESTRICTION FOR HEALTH AND SURVIVAL

Abstract Emerging new evidence highlights the importance of prolonged daily fasting periods for the health and survival benefits of calorie restriction (CR) and time-restricted feeding (TRF) in male mice; however, little is known about the impact of these feeding regimens in females. Using a carousel feeder system that enables controlling the duration, amount, and timing of food availability, we show that mice on CR had a robust physiological response and decreased progression of malignant neoplasms and severity of inflammatory diseases in the lung compared to TRF. CR is associated with a unique serum metabolomics signature in overnight-fasted animals compared to TRF. The systemic impact of CR and TRF regimens measured from covariation of serum metabolites with energetics and healthspan metrics indicates that daytime (rest-phase) feeding with prolonged fasting periods initiated late in life confers greater benefits when combined with an imposed lower energy intake.