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

2020 ◽  
Vol 5 (4) ◽  
pp. 33-44
Author(s):  
A. V. Panov ◽  
S. I. Dikalov ◽  
M. A. Darenskaya ◽  
L. V. Rychkova ◽  
L. I. Kolesnikova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Cardiovascular Diseases ◽  
Developed Countries ◽  
Biologically Active ◽  
Racemic Mixture ◽  
New Paradigm ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Perhydroxyl Radical

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.

scholarly journals Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

scholarly journals Oxidative stress in ageing

2017 ◽  
Vol 5 (11) ◽  
pp. 4826 ◽  
Author(s):  
Fasna K. A. ◽  
Geetha N. ◽  
Jean Maliekkal
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Free Radicals ◽  
Free Radical ◽  
Age Groups ◽  
The Body ◽  
Antioxidant Systems ◽  
Lipid Peroxidation Product ◽  
Free Radical Theory ◽  
Radical Theory

Background: Ageing is characterized by a gradual decline in body functions and decreased ability to maintain homeostasis. The free radical theory of ageing proposed by Harman D states that ageing is a result of cumulative damage incurred by free radical reactions. Free radicals are highly reactive molecular species with unpaired electrons; generated in the body by several physiological processes. Prime target to free radical attack are the polyunsaturated fatty acids of cell membranes causing lipid peroxidation. The free radicals are neutralized by the exogenous and endogenous antioxidant systems. Oxidative stress occurs when large number of free radicals are produced or the antioxidant activity is impaired. The present study is focused to find out the role of oxidative stress in ageing.Methods: A cross sectional observational study was undertaken to assess the oxidative stress in ageing; by determining the levels of lipid peroxidation product- malondialdehyde (MDA), the antioxidants- superoxide dismutase (SOD) and ceruloplasmin in various age groups. 150 healthy subjects were selected randomly and categorised into three different age groups of 20-30 years, 40-59 years and 60-90 years; with 50 subjects in each group. Results were expressed as mean ± standard deviation.Results: a significant elevation in serum MDA level and a decline in SOD were observed in 40-59 years and 60-90 years age groups. However, an elevated ceruloplasmin level was found in the above age groups.Conclusions: Aforementioned observations are suggestive of an association between oxidative stress and the progression of ageing process.

scholarly journals Oxidative Stress and Longevity in Okinawa: An Investigation of Blood Lipid Peroxidation and Tocopherol in Okinawan Centenarians

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Makoto Suzuki ◽  
D. Craig Willcox ◽  
Matthew W. Rosenbaum ◽  
Bradley J. Willcox
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Vitamin E ◽  
Age Groups ◽  
Plasma Lipid ◽  
Lipid Peroxide ◽  
Human Longevity ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Theory Of Aging

Background. The Free Radical Theory of Aging mechanistically links oxidative stress to aging. Okinawa has among the world's longest-lived populations but oxidative stress in this population has not been well characterized.Methods. We compared plasma lipid peroxide (LPO) and vitamin E—plasma and intracellular tocopherol levels (total α, β, and γ), in centenarians with younger controls.Results. Both LPO and vitamin E tocopherols were lower in centenarians, with the exception of intracellular β-tocopherol, which was significantly higher in centenarians versus younger controls. There were no significant differences between age groups for tocopherol: cholesterol and tocopherol: LPO ratios. Correlations were found between α-Tocopherol and LPO in septuagenarians but not in centenarians.Conclusions. The low plasma level of LPO in Okinawan centenarians, compared to younger controls, argues for protection against oxidative stress in the centenarian population and is consistent with the predictions of the Free Radical Theory of Aging. However, the present work does not strongly support a role for vitamin E in this phenomenon. The role of intracellular β-tocopherol deserves additional study. More research is needed on the contribution of oxidative stress and antioxidants to human longevity.

scholarly journals Mitochondria, oxidative stress and aging

2014 ◽  
Vol 155 (12) ◽  
pp. 447-452
Author(s):  
András Szarka ◽  
Gábor Bánhegyi ◽  
Balázs Sümegi
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Dna ◽  
Mitochondrial Respiration ◽  
Accelerated Aging ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Vicious Cycle ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Theory Of Aging

The free radical theory of aging was defined in the 1950s. On the base of this theory, the reactive oxygen species formed in the metabolic pathways can play pivotal role in ageing. The theory was modified by defining the mitochondrial respiration as the major cellular source of reactive oxygen species and got the new name mitochondrial theory of aging. Later on the existence of a “vicious cycle” was proposed, in which the reactive oxygen species formed in the mitochondrial respiration impair the mitochondrial DNA and its functions. The formation of reactive oxygen species are elevated due to mitochondrial dysfunction. The formation of mitochondrial DNA mutations can be accelerated by this “vicious cycle”, which can lead to accelerated aging. The exonuclease activity of DNA polymerase γ, the polymerase responsible for the replication of mitochondrial DNA was impaired in mtDNA mutator mouse recently. The rate of somatic mutations in mitochondrial DNA was elevated and an aging phenotype could have been observed in these mice. Surprisingly, no oxidative impairment neither elevated reactive oxygen species formation could have been observed in the mtDNA mutator mice, which may question the existence of the “vicious cycle”. Orv. Hetil., 2014, 155(12), 447–452.

Grape seed flour (GSF) extends longevity by improving multi-organ dysfunction and age-associated oxidative stress and inflammation in healthy rat

2021 ◽  
Author(s):  
Khawla Jebari ◽  
Kamel Charradi ◽  
Mohamed Mahmoudi ◽  
Safwen Kadri ◽  
Mossadok Ben-Attia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Grape Seed ◽  
Nutritional Supplement ◽  
Premature Aging ◽  
High Dose ◽  
Biological Macromolecules ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Seed Flour ◽  
Natural Medicine

Abstract According to the free radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout lifespan leads to impairment of the main biological macromolecules as DNA, lipids and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anti-carcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong lifespan of Wistar rats when administered from early life (one month-old animals) till their natural death. Data clearly show that high dose GSF extends organism longevity and healthspan by improving multi-organ damages, systemic fuelling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation, is currently under investigation.

scholarly journals Markers of Oxidative Stress in Erythrocytes and Plasma During Aging in Humans

2010 ◽  
Vol 3 (1) ◽  
pp. 2-12 ◽  
Author(s):  
Kanti Bhooshan Pandey ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Biological Process ◽  
Related Phenomenon ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Age Related ◽  
General Decline ◽  
Markers Of Oxidative Stress ◽  
Probability Of Death

Aging is an inevitable universal biological process, which can be characterized by a general decline in physiological function with the accumulation of diverse adverse changes and increased probability of death. Among several theories, oxidative stress/free radical theory offers the best mechanistic elucidation of the aging process and other age-related phenomenon. In the present paper, we discuss the aging process and have focused on the importance of some reliable markers of oxidative stress which may be used as biomarkers of the aging process.

scholarly journals MicroRNA Regulation of Oxidative Stress-Induced Cellular Senescence

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Huaije Bu ◽  
Sophia Wedel ◽  
Maria Cavinato ◽  
Pidder Jansen-Dürr
Keyword(s):  
Oxidative Stress ◽  
Cellular Senescence ◽  
Cellular Tissue ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Microrna Regulation ◽  
Age Related ◽  
Epigenetic Events ◽  
Permanent Cell ◽  
Theory Of Aging

Aging is a time-related process of functional deterioration at cellular, tissue, organelle, and organismal level that ultimately brings life to end. Cellular senescence, a state of permanent cell growth arrest in response to cellular stress, is believed to be the driver of the aging process and age-related disorders. The free radical theory of aging, referred to as oxidative stress (OS) theory below, is one of the most studied aging promoting mechanisms. In addition, genetics and epigenetics also play large roles in accelerating and/or delaying the onset of aging and aging-related diseases. Among various epigenetic events, microRNAs (miRNAs) turned out to be important players in controlling OS, aging, and cellular senescence. miRNAs can generate rapid and reversible responses and, therefore, are ideal players for mediating an adaptive response against stress through their capacity to fine-tune gene expression. However, the importance of miRNAs in regulating OS in the context of aging and cellular senescence is largely unknown. The purpose of our article is to highlight recent advancements in the regulatory role of miRNAs in OS-induced cellular senescence.

scholarly journals Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1006
Author(s):  
Ilenia Martinelli ◽  
Daniele Tomassoni ◽  
Proshanta Roy ◽  
Lorenzo Di Cesare Mannelli ◽  
Francesco Amenta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Properties ◽  
Organ Damage ◽  
Nutritional Supplement ◽  
Left Ventricular ◽  
Biologically Active ◽  
Racemic Mixture ◽  
Spontaneously Hypertensive ◽  
Effect Of Treatment ◽  
Immunohistochemical Techniques

Renal and cardiac impairments are frequent events in the presence of hypertension. Organ damage is mainly linked to oxidative stress due to high blood pressure and may be reduced by antioxidant supplementation. Alpha-lipoic acid (ALA) is one of most effective antioxidants. It is widely used as a nutritional supplement in a racemic mixture (+/–), even though the (+)-enantiomer is biologically active. This study was designed to investigate the effect of treatment with (+/–)-ALA and its enantiomers on renal and heart parenchyma in spontaneously hypertensive rats (SHR), using immunochemical and immunohistochemical techniques. The results confirmed that the oxidative mechanisms of organ alterations, due to hypertension, and characterized by glomerular and tubular lesions, left ventricular hypertrophy, and fibrosis but not by apoptosis were accompanied by proteins’ and nucleic acids’ oxidation. We found greater effectiveness of (+)-ALA compared to (+/−)-ALA in reducing oxidative stress, cardiac and renal damages in SHR. To conclude, these data propose (+)-ALA as one of the more appropriate antioxidant molecules to prevent renal and cardiac alterations associated with hypertension.

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