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

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...

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Autores principales: Hwangbo, Dae-Sung, Lee, Hye-Yeon, Abozaid, Leen Suleiman, Min, Kyung-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230387/
https://www.ncbi.nlm.nih.gov/pubmed/32344591
http://dx.doi.org/10.3390/nu12041194
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author Hwangbo, Dae-Sung
Lee, Hye-Yeon
Abozaid, Leen Suleiman
Min, Kyung-Jin
author_facet Hwangbo, Dae-Sung
Lee, Hye-Yeon
Abozaid, Leen Suleiman
Min, Kyung-Jin
author_sort Hwangbo, Dae-Sung
collection PubMed
description 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.
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spelling pubmed-72303872020-05-22 Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms Hwangbo, Dae-Sung Lee, Hye-Yeon Abozaid, Leen Suleiman Min, Kyung-Jin Nutrients Review 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. MDPI 2020-04-24 /pmc/articles/PMC7230387/ /pubmed/32344591 http://dx.doi.org/10.3390/nu12041194 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hwangbo, Dae-Sung
Lee, Hye-Yeon
Abozaid, Leen Suleiman
Min, Kyung-Jin
Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
title Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
title_full Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
title_fullStr Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
title_full_unstemmed Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
title_short Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms
title_sort mechanisms of lifespan regulation by calorie restriction and intermittent fasting in model organisms
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230387/
https://www.ncbi.nlm.nih.gov/pubmed/32344591
http://dx.doi.org/10.3390/nu12041194
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