scholarly journals GLUTATHIONE DEFICIENCY AND OXIDATIVE STRESS IN AGING: METABOLIC MECHANISM AND TARGETED INTERVENTION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S416-S416
Author(s):  
Farook Jahoor ◽  
George E Taffet ◽  
Rajagopal V Sekhar
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Functional Decline ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Isotope Tracer ◽  
Age Related ◽  
Theory Of Aging ◽  
Metabolic Mechanism ◽  
Glutathione Deficiency

Abstract The free-radical theory of aging suggests that age-related functional decline is mediated by increases in free-radical induced oxidative-stress. Cells normally depend on antioxidants for protection against oxidative-stress. Glutathione is the most abundant endogenous intracellular antioxidant protein composed of 3 amino-acids, cysteine, glycine and glutamic-acid, and is known to be deficient in older-humans. We investigated Glutathione kinetics in older humans using a stable-isotope tracer-based approach, and found that compared to younger humans, older-humans had severe Glutathione deficiency as a result of decreased synthesis caused by limited availability of glycine and cysteine, and associated with elevated oxidative-stress. Orally supplementing glycine and cysteine (provided as N-acetylcysteine) at doses of 1.33mmol/kg/d and 0.81mmol/kg/d respectively for 2-weeks corrected their intracellular deficiency, normalized Glutathione synthesis rates and lowered oxidative-stress to levels in younger controls. These results suggest that short-term supplementation of GlyNAC at these doses can successfully correct intracellular Glutathione deficiency in older-humans.

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 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 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 Recent Review on Oxidative stress, Cellular senescence and Age-Associated Diseases

2020 ◽  
Vol 11 (2) ◽  
pp. 1331-1342
Author(s):  
Nandita H ◽  
Manohar M ◽  
Gowda DV
Keyword(s):  
Oxidative Stress ◽  
Cellular Senescence ◽  
Tumor Development ◽  
Cellular Level ◽  
The Novel ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Age Related ◽  
Theory Of Aging ◽  
Main Factor

Reactive Oxygen Species (ROS) is considered as the main factor of the Free Radical theory of aging over centuries and it indicates the pathophysiology of aging in mammals. ROS causes oxidative stress, which is a major component in the aging process of higher organisms. ROS also leads to many age-related diseases such as cancer, cardiovascular disease, diabetes, etc. ROS causes damage to most of the biological membranes that cause these chronic diseases. Enhanced ROS levels at the cellular level lead to cellular senescence. It is a stage of cells where growth arrest happens associated with the secretion of Senescence-associated secretory phenotype (SASP) factors. Senescence maintains tissue homeostasis, functions in normal development and restricts tumor development. In this regard, recent experimental evidence has shown that the genetic or pharmacological ablation of senescent cells extends the life span and improves the healthspan. Here, we review the cellular and molecular links between cellular senescence and aging and discuss the novel therapeutic avenues that this connection opens.

scholarly journals OXIDATIVE STRESS IN AGING

2020 ◽  
pp. 10-22
Author(s):  
Н. К. Зенков ◽  
П. М. Кожин ◽  
А. В. Чечушков ◽  
Н. В. Кандалинцева ◽  
Г. Г. Мартинович ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanisms ◽  
Redox Balance ◽  
Ros Generation ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Age Related ◽  
Theory Of Aging ◽  
Autophagy Activity ◽  
Important System

Выдвинутая более 50 лет назад Д. Харманом свободнорадикальная теория старения остается популярной и сегодня. В обзоре проведен анализ возрастных изменений основных эндогенных механизмов продукции активированных кислородных метаболитов (АКМ) и механизмов антиоксидантной защиты. С возрастом генерация АКМ митохондриями, пероксисомами и NAD(P) H -оксидазами усиливается, в то время как транскрипционная активность важной системы поддержания редокс-баланса Keap 1/ Nrf 2/ ARE уменьшается. У старых животных отмечается также низкая активность аутофагии, удаляющей из клеток поврежденные органеллы и агрегированные структуры. Возрастное смещение редокс-баланса в сторону окислительного стресса может являться причиной развития возраст-ассоциированных нейрогеденеративных, аутоиммунных и воспалительных патологий. The free-radical theory of aging, advanced more than 50 years ago by D. Harman, remains popular today. The review analyzes age-related changes in the main endogenous mechanisms of reactive oxygen species (ROS) production and antioxidant defense mechanisms. With age, ROS generation by mitochondria, peroxisomes, and NAD(P)H oxidases is enhanced, while the transcriptional activity of the important system Keap 1/ Nrf 2/ ARE maintaining redox balance decreases. In old animals, autophagy activity is also low, which removes damaged organelles and aggregated structures from cells. The age-related shift of the redox balance towards oxidative stress can cause the development of age-associated neurodegenerative, autoimmune and infl ammatory pathologies.

The Free Radical Theory of Aging In Search of a Strategy for Increasing Life Span / Свободнорадикальная Теория О Старении В Поиске Стратегии Увеличить Продолжительность Жизни

Folia Medica ◽  
2013 ◽  
Vol 55 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Diana G. Ivanova ◽  
Tatyana M. Yankova
Keyword(s):  
Free Radical ◽  
Life Activity ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Progressive Decline ◽  
Stress Theory ◽  
Age Related ◽  
Tissue Changes ◽  
Theory Of Aging

Abstract This overview is an attempt to throw a fresh look at the popular free radical theory of aging (referred to also as oxidative stress theory) which holds that the progressive decline in physiological functions is a result of accumulation of diverse deleterious changes caused by reactive oxygen species (ROS). We discuss the role of mitochondria as a major source of ROS in the cell and how these link accumulation of oxidative damage to the age-related changes in physiologic functions. The free radical theory of aging is analysed here from two different views of aging - one (the pessimistic view) that regards aging as the inevitable result of life activity the consequences of which are accumulation of errors in the genome and damage of the biomolecules, and the other (the optimistic view) which considers that it is the changes in mitochondrial pathways of apoptosis with age that cause the functional tissue changes and aging. We also discuss the possibility of delaying the aging process by appropriate diet or drug therapy, which includes also calorie restriction as a mechanism of modifying the generation of free radicals and body metabolism and thus extending lifespan as a result.

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