The importance of circadian alignment of feeding on longevity under calorie restriction has never been shown and experiments conducted in mice by Takahashi has studied the contributions of feeding time and fasting under calorie restriction (CR) and compared behavioral, metabolic, and molecular outcomes throughout the life span. The researchers are also looking for small molecule modulators of CLOCK–BMAL1. The authors discuss whether time-restricted feeding without CR can extend lifespan and the authors are trying to rescue this age-related decline by using time-restricted feeding and by enhancing the expression of the master circadian control gene Clock (using transgenic mice).
RELEVANT REFERENCES:
1. Acosta-Rodríguez V, Rijo-Ferreira F, Izumo M, Xu P, Wight-Carter M, Green CB, Takahashi JS. Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice. Science. 2022 Jun 10;376(6598):1192-1202.
2. Greenhill, C. Timing of feeding for longevity in mice. Nat Rev Endocrinol (2022).
3. SIRT1 is a circadian deacetylase for core clock components. Cell, Belden, W. J., & Dunlap, J. C. (2008). 134(2), 212–214.
4. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, Schibler U. Cell. 2008 Jul 25;134(2):317-28.
5. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Chang, H. C., & Guarente, L. (2013). Cell, 153(7), 1448–1460.
6. Appetite dysregulation and obesity in Western Countries
7. C. Nutrition Therapy Regulates Caffeine Metabolism with Relevance to NAFLD and Induction of Type 3 Diabetes. J Diabetes Metab Disord. 2017; 4: 019.
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