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A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3
This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Pleiades Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033555/ https://www.ncbi.nlm.nih.gov/pubmed/33941065 http://dx.doi.org/10.1134/S0006297921040052 |
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author | Shilovsky, Gregory A. Putyatina, Tatyana S. Morgunova, Galina V. Seliverstov, Alexander V. Ashapkin, Vasily V. Sorokina, Elena V. Markov, Alexander V. Skulachev, Vladimir P. |
author_facet | Shilovsky, Gregory A. Putyatina, Tatyana S. Morgunova, Galina V. Seliverstov, Alexander V. Ashapkin, Vasily V. Sorokina, Elena V. Markov, Alexander V. Skulachev, Vladimir P. |
author_sort | Shilovsky, Gregory A. |
collection | PubMed |
description | This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2 enables stress adaptation by activating cell antioxidant defense and other metabolic processes via control of expression of over 200 target genes in response to various types of stress. The GSK3 system represents a “regulating valve” that controls fine oscillations in the Nrf2 level, unlike Keap1, which prevents significant changes in the Nrf2 content in the absence of oxidative stress and which is inactivated by the oxidative stress. Furthermore, GSK3 modifies core circadian clock proteins (Bmal1, Clock, Per, Cry, and Rev-erbα). Phosphorylation by GSK3 leads to the inactivation and degradation of circadian rhythm-activating proteins (Bmal1 and Clock) and vice versa to the activation and nuclear translocation of proteins suppressing circadian rhythms (Per and Rev-erbα) with the exception of Cry protein, which is likely to be implicated in the fine tuning of biological clock. Functionally, GSK3 appears to be one of the hubs in the cross-regulation of circadian rhythms and antioxidant defense. Here, we present the data on the crosstalk between the most powerful cell antioxidant mechanism, the Nrf2 system, and the biorhythm-regulating system in mammals, including the impact of GSK3 overexpression and knockout on the Nrf2 signaling. Understanding the interactions between the regulatory cascades linking homeostasis maintenance and cell response to oxidative stress will help in elucidating molecular mechanisms that underlie aging and longevity. |
format | Online Article Text |
id | pubmed-8033555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Pleiades Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-80335552021-04-09 A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3 Shilovsky, Gregory A. Putyatina, Tatyana S. Morgunova, Galina V. Seliverstov, Alexander V. Ashapkin, Vasily V. Sorokina, Elena V. Markov, Alexander V. Skulachev, Vladimir P. Biochemistry (Mosc) Review This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2 enables stress adaptation by activating cell antioxidant defense and other metabolic processes via control of expression of over 200 target genes in response to various types of stress. The GSK3 system represents a “regulating valve” that controls fine oscillations in the Nrf2 level, unlike Keap1, which prevents significant changes in the Nrf2 content in the absence of oxidative stress and which is inactivated by the oxidative stress. Furthermore, GSK3 modifies core circadian clock proteins (Bmal1, Clock, Per, Cry, and Rev-erbα). Phosphorylation by GSK3 leads to the inactivation and degradation of circadian rhythm-activating proteins (Bmal1 and Clock) and vice versa to the activation and nuclear translocation of proteins suppressing circadian rhythms (Per and Rev-erbα) with the exception of Cry protein, which is likely to be implicated in the fine tuning of biological clock. Functionally, GSK3 appears to be one of the hubs in the cross-regulation of circadian rhythms and antioxidant defense. Here, we present the data on the crosstalk between the most powerful cell antioxidant mechanism, the Nrf2 system, and the biorhythm-regulating system in mammals, including the impact of GSK3 overexpression and knockout on the Nrf2 signaling. Understanding the interactions between the regulatory cascades linking homeostasis maintenance and cell response to oxidative stress will help in elucidating molecular mechanisms that underlie aging and longevity. Pleiades Publishing 2021-04-09 2021 /pmc/articles/PMC8033555/ /pubmed/33941065 http://dx.doi.org/10.1134/S0006297921040052 Text en © Pleiades Publishing, Ltd. 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Review Shilovsky, Gregory A. Putyatina, Tatyana S. Morgunova, Galina V. Seliverstov, Alexander V. Ashapkin, Vasily V. Sorokina, Elena V. Markov, Alexander V. Skulachev, Vladimir P. A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3 |
title | A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3 |
title_full | A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3 |
title_fullStr | A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3 |
title_full_unstemmed | A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3 |
title_short | A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3 |
title_sort | crosstalk between the biorhythms and gatekeepers of longevity: dual role of glycogen synthase kinase-3 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033555/ https://www.ncbi.nlm.nih.gov/pubmed/33941065 http://dx.doi.org/10.1134/S0006297921040052 |
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