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Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms

Department of Biology, University of Louisville, Louisville, KY 40292, USA
Department of Biological Sciences, Inha University, Incheon 22212, Korea
Authors to whom correspondence should be addressed.
Equal contributions were made by these authors.
Nutrients 2020, 12(4), 1194;
Received: 31 March 2020 / Revised: 19 April 2020 / Accepted: 22 April 2020 / Published: 24 April 2020
Genetic and pharmacological interventions have successfully extended healthspan and lifespan in animals, but their genetic interventions are not appropriate options for human applications and pharmacological intervention needs more solid clinical evidence. Consequently, dietary manipulations are the only practical and probable strategies to promote health and longevity in humans. Caloric restriction (CR), reduction of calorie intake to a level that does not compromise overall health, has been considered as being one of the most promising dietary interventions to extend lifespan in humans. Although it is straightforward, continuous reduction of calorie or food intake is not easy to practice in real lives of humans. Recently, fasting-related interventions such as intermittent fasting (IF) and time-restricted feeding (TRF) have emerged as alternatives of CR. Here, we review the history of CR and fasting-related strategies in animal models, discuss the molecular mechanisms underlying these interventions, and propose future directions that can fill the missing gaps in the current understanding of these dietary interventions. CR and fasting appear to extend lifespan by both partially overlapping common mechanisms such as the target of rapamycin (TOR) pathway and circadian clock, and distinct independent mechanisms that remain to be discovered. We propose that a systems approach combining global transcriptomic, metabolomic, and proteomic analyses followed by genetic perturbation studies targeting multiple candidate pathways will allow us to better understand how CR and fasting interact with each other to promote longevity. View Full-Text
Keywords: aging; lifespan; longevity; calorie restriction; fasting aging; lifespan; longevity; calorie restriction; fasting
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Hwangbo, D.-S.; Lee, H.-Y.; Abozaid, L.S.; Min, K.-J. Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms. Nutrients 2020, 12, 1194.

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