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Genome-Protecting Compounds as Potential Geroprotectors

Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increas...

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Autores principales: Proshkina, Ekaterina, Shaposhnikov, Mikhail, Moskalev, Alexey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350017/
https://www.ncbi.nlm.nih.gov/pubmed/32599754
http://dx.doi.org/10.3390/ijms21124484
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author Proshkina, Ekaterina
Shaposhnikov, Mikhail
Moskalev, Alexey
author_facet Proshkina, Ekaterina
Shaposhnikov, Mikhail
Moskalev, Alexey
author_sort Proshkina, Ekaterina
collection PubMed
description Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.
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spelling pubmed-73500172020-07-21 Genome-Protecting Compounds as Potential Geroprotectors Proshkina, Ekaterina Shaposhnikov, Mikhail Moskalev, Alexey Int J Mol Sci Review Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction. MDPI 2020-06-24 /pmc/articles/PMC7350017/ /pubmed/32599754 http://dx.doi.org/10.3390/ijms21124484 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
Proshkina, Ekaterina
Shaposhnikov, Mikhail
Moskalev, Alexey
Genome-Protecting Compounds as Potential Geroprotectors
title Genome-Protecting Compounds as Potential Geroprotectors
title_full Genome-Protecting Compounds as Potential Geroprotectors
title_fullStr Genome-Protecting Compounds as Potential Geroprotectors
title_full_unstemmed Genome-Protecting Compounds as Potential Geroprotectors
title_short Genome-Protecting Compounds as Potential Geroprotectors
title_sort genome-protecting compounds as potential geroprotectors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350017/
https://www.ncbi.nlm.nih.gov/pubmed/32599754
http://dx.doi.org/10.3390/ijms21124484
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