Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction

Dietary restriction (DR), which is defined as a reduction of particular or total nutrient intake without causing malnutrition, has been proved to be a robust way to extend both lifespan and health-span in various species from yeast to mammal. However, the molecular mechanisms by which DR confers ben...

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Main Authors: Yizhou Jiang, Fengxia Yan, Zhongping Feng, Philip Lazarovici, Wenhua Zheng
Format: Article
Language:English
Published: MDPI AG 2019-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/9/1/100
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author Yizhou Jiang
Fengxia Yan
Zhongping Feng
Philip Lazarovici
Wenhua Zheng
author_facet Yizhou Jiang
Fengxia Yan
Zhongping Feng
Philip Lazarovici
Wenhua Zheng
author_sort Yizhou Jiang
collection DOAJ
description Dietary restriction (DR), which is defined as a reduction of particular or total nutrient intake without causing malnutrition, has been proved to be a robust way to extend both lifespan and health-span in various species from yeast to mammal. However, the molecular mechanisms by which DR confers benefits on longevity were not yet fully elucidated. The forkhead box O transcription factors (FOXOs), identified as downstream regulators of the insulin/IGF-1 signaling pathway, control the expression of many genes regulating crucial biological processes such as metabolic homeostasis, redox balance, stress response and cell viability and proliferation. The activity of FOXOs is also mediated by AMP-activated protein kinase (AMPK), sirtuins and the mammalian target of rapamycin (mTOR). Therefore, the FOXO-related pathways form a complex network critical for coordinating a response to environmental fluctuations in order to maintain cellular homeostasis and to support physiological aging. In this review, we will focus on the role of FOXOs in different DR interventions. As different DR regimens or calorie (energy) restriction mimetics (CRMs) can elicit both distinct and overlapped DR-related signaling pathways, the benefits of DR may be maximized by combining diverse forms of interventions. In addition, a better understanding of the precise role of FOXOs in different mechanistic aspects of DR response would provide clear cellular and molecular insights on DR-induced increase of lifespan and health-span.
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spelling doaj.art-7f196e2d08c94169b7d158fbb8eedd782023-09-02T20:10:18ZengMDPI AGCells2073-44092019-12-019110010.3390/cells9010100cells9010100Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary RestrictionYizhou Jiang0Fengxia Yan1Zhongping Feng2Philip Lazarovici3Wenhua Zheng4Centre of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Macau 999078, ChinaSchool of Medical Science, Jinan University, Guangzhou 510080, ChinaDepartment of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, CanadaSchool of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, IsraelCentre of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Macau 999078, ChinaDietary restriction (DR), which is defined as a reduction of particular or total nutrient intake without causing malnutrition, has been proved to be a robust way to extend both lifespan and health-span in various species from yeast to mammal. However, the molecular mechanisms by which DR confers benefits on longevity were not yet fully elucidated. The forkhead box O transcription factors (FOXOs), identified as downstream regulators of the insulin/IGF-1 signaling pathway, control the expression of many genes regulating crucial biological processes such as metabolic homeostasis, redox balance, stress response and cell viability and proliferation. The activity of FOXOs is also mediated by AMP-activated protein kinase (AMPK), sirtuins and the mammalian target of rapamycin (mTOR). Therefore, the FOXO-related pathways form a complex network critical for coordinating a response to environmental fluctuations in order to maintain cellular homeostasis and to support physiological aging. In this review, we will focus on the role of FOXOs in different DR interventions. As different DR regimens or calorie (energy) restriction mimetics (CRMs) can elicit both distinct and overlapped DR-related signaling pathways, the benefits of DR may be maximized by combining diverse forms of interventions. In addition, a better understanding of the precise role of FOXOs in different mechanistic aspects of DR response would provide clear cellular and molecular insights on DR-induced increase of lifespan and health-span.https://www.mdpi.com/2073-4409/9/1/100foxodietary restrictioninsulin/igf-1 signaling pathwayampksirtuinsmtorlongevitycalorie restriction mimetics
spellingShingle Yizhou Jiang
Fengxia Yan
Zhongping Feng
Philip Lazarovici
Wenhua Zheng
Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
Cells
foxo
dietary restriction
insulin/igf-1 signaling pathway
ampk
sirtuins
mtor
longevity
calorie restriction mimetics
title Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
title_full Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
title_fullStr Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
title_full_unstemmed Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
title_short Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction
title_sort signaling network of forkhead family of transcription factors foxo in dietary restriction
topic foxo
dietary restriction
insulin/igf-1 signaling pathway
ampk
sirtuins
mtor
longevity
calorie restriction mimetics
url https://www.mdpi.com/2073-4409/9/1/100
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