Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm

Cardiovascular diseases are among the major causes of mortality among aged people in most developed countries. Oxidative stress, which causes mutations of mitochondrial DNA and mitochondrial dysfunctions, was considered as the main mechanism of heart failure and other pathologies of old age. However...

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Autores principales:	A. V. Panov, S. I. Dikalov, M. A. Darenskaya, L. V. Rychkova, L. I. Kolesnikova, S. I. Kolesnikov
Formato:	article
Lenguaje:	RU
Publicado:	Scientific Сentre for Family Health and Human Reproduction Problems 2020
Materias:	mitochondria aging metabolic syndrome oxidative stress cardiolipin phosphatidylethanolamine isoprostane lipid peroxidation isolevuglandins Science Q
Acceso en línea:	https://doaj.org/article/807c1ade000e406c8c16eb3f3a0b2fbe
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spelling	oai:doaj.org-article:807c1ade000e406c8c16eb3f3a0b2fbe2021-11-23T06:14:44ZMitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm2541-94202587-959610.29413/ABS.2020-5.4.5https://doaj.org/article/807c1ade000e406c8c16eb3f3a0b2fbe2020-09-01T00:00:00Zhttps://www.actabiomedica.ru/jour/article/view/2390https://doaj.org/toc/2541-9420https://doaj.org/toc/2587-9596Cardiovascular diseases are among the major causes of mortality among aged people in most developed countries. Oxidative stress, which causes mutations of mitochondrial DNA and mitochondrial dysfunctions, was considered as the main mechanism of heart failure and other pathologies of old age. However, in recent years the prior paradigm of mechanisms of aging, oxidative stress and antioxidative defense was questioned and in some aspects even turned out to be wrong. In this review, we discuss the new data that led to the need to reconsider paradigms. We show that although the mitochondrial free radical theory of aging remains valid, the radical responsible for the aging is the protonated form of the superoxide radical, namely perhydroxyl radical, which was largely ignored all previous years. Perhydroxyl radical initiates the isoprostane pathway of lipid peroxidation (IPLP) of polyunsaturated fatty acids, which are part of the phospholipid core of the mitochondrial inner membrane. IPLP was discovered 30 years ago by Roberts and Morrow at the Vanderbilt University, but the mechanism of its initiation remained unknown. The IPLP causes formation of the racemic mixture of hundreds of biologically active products, named isoprostanes, and highly toxic molecules, first of all isolevuglandins. We distinguish two types of damages caused by IPLP during aging. The first one is associated with oxidative damages to cardiolipin and phosphatidylethanolamine (PEA), which result in disruption of polyenzymatic complexes of the oxidative phosphorylation system. The second type of dysfunctions is caused by the direct actions of toxic products on the lysine-containing proteins and PEA. To this type of mitochondrial damages evidently belongs the oxidative damage of the mitochondrial DNA polymerase, which results in a 20-fold increase in mutations of mitochondrial mtDNA.A. V. PanovS. I. DikalovM. A. DarenskayaL. V. RychkovaL. I. KolesnikovaS. I. KolesnikovScientific Сentre for Family Health and Human Reproduction Problemsarticlemitochondriaagingmetabolic syndromeoxidative stresscardiolipinphosphatidylethanolamineisoprostane lipid peroxidationisolevuglandinsScienceQRUActa Biomedica Scientifica, Vol 5, Iss 4, Pp 33-44 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	mitochondria aging metabolic syndrome oxidative stress cardiolipin phosphatidylethanolamine isoprostane lipid peroxidation isolevuglandins Science Q
spellingShingle	mitochondria aging metabolic syndrome oxidative stress cardiolipin phosphatidylethanolamine isoprostane lipid peroxidation isolevuglandins Science Q A. V. Panov S. I. Dikalov M. A. Darenskaya L. V. Rychkova L. I. Kolesnikova S. I. Kolesnikov Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm
description	Cardiovascular diseases are among the major causes of mortality among aged people in most developed countries. Oxidative stress, which causes mutations of mitochondrial DNA and mitochondrial dysfunctions, was considered as the main mechanism of heart failure and other pathologies of old age. However, in recent years the prior paradigm of mechanisms of aging, oxidative stress and antioxidative defense was questioned and in some aspects even turned out to be wrong. In this review, we discuss the new data that led to the need to reconsider paradigms. We show that although the mitochondrial free radical theory of aging remains valid, the radical responsible for the aging is the protonated form of the superoxide radical, namely perhydroxyl radical, which was largely ignored all previous years. Perhydroxyl radical initiates the isoprostane pathway of lipid peroxidation (IPLP) of polyunsaturated fatty acids, which are part of the phospholipid core of the mitochondrial inner membrane. IPLP was discovered 30 years ago by Roberts and Morrow at the Vanderbilt University, but the mechanism of its initiation remained unknown. The IPLP causes formation of the racemic mixture of hundreds of biologically active products, named isoprostanes, and highly toxic molecules, first of all isolevuglandins. We distinguish two types of damages caused by IPLP during aging. The first one is associated with oxidative damages to cardiolipin and phosphatidylethanolamine (PEA), which result in disruption of polyenzymatic complexes of the oxidative phosphorylation system. The second type of dysfunctions is caused by the direct actions of toxic products on the lysine-containing proteins and PEA. To this type of mitochondrial damages evidently belongs the oxidative damage of the mitochondrial DNA polymerase, which results in a 20-fold increase in mutations of mitochondrial mtDNA.
format	article
author	A. V. Panov S. I. Dikalov M. A. Darenskaya L. V. Rychkova L. I. Kolesnikova S. I. Kolesnikov
author_facet	A. V. Panov S. I. Dikalov M. A. Darenskaya L. V. Rychkova L. I. Kolesnikova S. I. Kolesnikov
author_sort	A. V. Panov
title	Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm
title_short	Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm
title_full	Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm
title_fullStr	Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm
title_full_unstemmed	Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm
title_sort	mitochondria: aging, metabolic syndrome and cardiovascular diseases. formation of a new paradigm
publisher	Scientific Сentre for Family Health and Human Reproduction Problems
publishDate	2020
url	https://doaj.org/article/807c1ade000e406c8c16eb3f3a0b2fbe
work_keys_str_mv	AT avpanov mitochondriaagingmetabolicsyndromeandcardiovasculardiseasesformationofanewparadigm AT sidikalov mitochondriaagingmetabolicsyndromeandcardiovasculardiseasesformationofanewparadigm AT madarenskaya mitochondriaagingmetabolicsyndromeandcardiovasculardiseasesformationofanewparadigm AT lvrychkova mitochondriaagingmetabolicsyndromeandcardiovasculardiseasesformationofanewparadigm AT likolesnikova mitochondriaagingmetabolicsyndromeandcardiovasculardiseasesformationofanewparadigm AT sikolesnikov mitochondriaagingmetabolicsyndromeandcardiovasculardiseasesformationofanewparadigm
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Mitochondria: Aging, Metabolic Syndrome and Cardiovascular Diseases. Formation of a New Paradigm

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