Some antioxidants studied as antiaging agents.

Some antioxidants studied as antiaging agents.

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If aging is due to or contributed by free radical reactions, as postulated by the free radical theory of aging, lifespan of organisms should be extended by administration of exogenous antioxidants. This paper reviews data on model organisms concerning the effects of exogenous antioxidants (antioxidant vitamins, lipoic acid, coenzyme Q, melatonin, r...

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... There is no clear evidence in human studies to support the beneficial effect of these supplements in relation to all-cause mortality, cardiovascular disease, cancer, or cognitive function [58]. In animal studies using mammalian models, many studies have shown that treatment with antioxidant supplements, when aimed at extending lifespan, result in no overt effect or even can have a negative effect [59]. ...
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Background The human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice, Cisd2 levels decrease during natural aging and genetic studies have shown that a high level of Cisd2 prolongs mouse lifespan and healthspan. Here, we evaluate the feasibility of using a Cisd2 activator as an effective way of delaying aging. Methods Hesperetin was identified as a promising Cisd2 activator by herb compound library screening. Hesperetin has no detectable toxicity based on in vitro and in vivo models. Naturally aged mice fed dietary hesperetin were used to investigate the effect of this Cisd2 activator on lifespan prolongation and the amelioration of age-related structural defects and functional decline. Tissue-specific Cisd2 knockout mice were used to study the Cisd2-dependent anti-aging effects of hesperetin. RNA sequencing was used to explore the biological effects of hesperetin on aging. Results Three discoveries are pinpointed. Firstly, hesperetin, a promising Cisd2 activator, when orally administered late in life, enhances Cisd2 expression and prolongs healthspan in old mice. Secondly, hesperetin functions mainly in a Cisd2-dependent manner to ameliorate age-related metabolic decline, body composition changes, glucose dysregulation, and organ senescence. Finally, a youthful transcriptome pattern is regained after hesperetin treatment during old age. Conclusions Our findings indicate that a Cisd2 activator, hesperetin, represents a promising and broadly effective translational approach to slowing down aging and promoting longevity via the activation of Cisd2.
... Antioxidants are dietary supplements taken for the protection against oxidative stress which also helps to delay the onset of agerelated diseases [8]. Several studies have administered antioxidant supplementation in rats to observe its potential benefits in delaying aging and protection from diseases [9,10]. Hesperidin (3,5,7 trihydroxyfavanone 7-rhamnoglucoside) is one such antioxidant polyphenol, a flavanone isolated from orange peels and abundantly found in citrus fruits [11]. ...
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Alternate day fasting (ADF) is beneficial in delaying aging and associated morbidities by reducing oxidative stress and inflammation. Hesperidin is a flavonoid antioxidant known for its antioxidant and anti-inflammatory properties. In this study, we aimed to evaluate the synergistic role of hesperidin supplementation and ADF regimen in Wistar rats on biomarkers of aging and inflammation. Middle-aged male Wistar rats (12–15 months) were divided into four groups (n = 6): Group I. Control (given 1.0 mL of carboxymethylcellulose orally); Group II. ADF (chow diet given on alternate days); Group III. Hesperidin (100 mg/kg BW orally); Group IV. ADF+ Hes (ADF regimen and hesperidin dupplemented) for three weeks. We measured clinical parameters and some crucial biomarkers of oxidative stress like FRAP, GSH, PMRS, MDA, PCO, AOPP, NO, insulin, adiponectin and inflammatory cytokines (TNF-α. IL-6, CRP and COX). A significant increase (p < 0.05) in insulin, FRAP and GSH, and a significant decrease (p < 0.05) in MDA and NO were observed in the ADF+Hes group. IL-6, CRP and COX were also significantly reduced (p < 0.05) suggesting hesperidin-induced benefits. We conclude that hesperidin intake during ADF may serve as a crucial purpose in improving signature biomarkers of health and metabolism.
... In the last decade, the correlation between antioxidant and age-related diseases has gained a lot of attention. Some researchers announced a positive correlation between antioxidants in drinks and longevity (Sadowska- Bartosz and Bartosz, 2014). EGCG could increase lifespan in several animal models such as Drosophila melanogaster (Wagner et al., 2015), Caenorhabditis elegans (Abbas and Wink, 2009), and Rattus norvegicus (Niu et al., 2013). ...
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Potential health benefits of tea has attracted significant scientific and public attention worldwide. Tea polyphenols are considered as natural promising complementary therapeutical agents for neurodegenerative diseases. However, the anti-neurodegeneration or anti-aging activities of oolong tea polyphenols have not been investigated. The current study aims to document beneficial effects of oolong tea polyphenols [dimers of epigallocatechin gallate (EGCG), oolonghomobisflavan A (OFA), and oolonghomobisflavan B (OFB)] with neuroprotective and neuritogenesis properties in cultured neuronal (Neuro-2a and HT22) cells and Caenorhabditis elegans models. In vitro , we found that the compounds (EGCG, OFA, and OFB) protect against glutamate-induced neurotoxicity via scavenging radical activity, suppression intracellular ROS and up-regulation of antioxidant enzymes. Moreover, the compounds induce neurite outgrowth via up-regulate Ten-4 gene expression. Interestingly, OFA and OFB exert stronger neuroprotective and neurite outgrowth properties than EGCG known as an excellent antioxidant agent in tea. In vivo , we found that the compounds protect against C. elegans Aβ-induced paralysis, chemotaxis deficiency and α-synuclein aggregation. Moreover, the compounds are capable of extending the lifespan of C. elegans. OFA and OFB possess both anti-neurodegeneration and anti-aging activities, supporting its therapeutic potential for the treatment of age-related neurodegenerative diseases which need to be studied in more detail in intervention studies.
... Specific behavior of nanoceria in biological objects can be beneficial for anti-ageing effect taking into account some experimental exceptions from freeradical theory as well (Gems and Doonan 2009). For example, overexpression of antioxidant enzymes, such as superoxide dismutase (SOD) or catalase as well as administration of antioxidant supplements do not extend lifespan (Jang et al. 2009;Sadowska-Bartosz and Bartosz 2014). On the contrary, ROS-mediated signalling in young and healthy organisms does not lead to lifespan decrease as was originally proposed by the mitochondrial free radical theory of aging (Barja 2013). ...
... It should be borne in mind that the use of antioxidants, especially in high concentrations, is not always effective in anti-aging therapy, as well as, the decrease in MC activity is not always adverse (Ristow and Schmeisser 2011;Sadowska-Bartosz and Bartosz 2014). According to the results of studies on C. elegans, under certain conditions, the development of oxidative stress leads to an increase in the survival and life span of nematodes, while the use of vitamins and antioxidants cancelled this effect (Yang and Hekimi 2010). ...
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Due to its unique redox chemistry, nanoceria is considered as potent free radical scavenger and antioxidant. However, their protective capacity in aging organisms remains controversial. To detect the anti-aging effects associated with the redox activity of 2 and 10 nm nano-CeO2, different test systems were used, including in vitro analysis, in situ assay of mitochondria function and in vivo studies of suitable nano-CeO2 on aging of male Wistar rats from 22 months-old to the end of life. The 2 nm nanoparticles exhibited not only antioxidant (·OH scavenging; chemiluminescence assay; decomposition of H2O2, phosphatidylcholine autooxidation) but also prooxidant properties (reduced glutathione and reduced nicotinamide adenine dinucleotide phosphate oxidation) as well as affected mitochondria whereas in most test systems 10 nm nano-CeO2 showed less activity or was inert. Prolonged use of the more redox active 2 nm nano-CeO2 (0.25–0.3 mg/kg/day) in vivo with drinking water resulted in improvement in physiological parameters and normalization of the prooxidant/antioxidant balance in liver and blood of aging animals. Survival analysis using Kaplan–Meier curve and Gehan tests with Yates' correction showed that by the time the prooxidant-antioxidant balance was assessed (32 months), survival rates exceeded the control values most considerably. The apparent median survival for the control rats was 900 days, and for the experimental rats—960 days. In general, the data obtained indicate the ability of extra-small 2 nm nano-CeO2 to improve quality of life and increase the survival rate of an aging organism.
... There is no clear evidence in human studies to support the beneficial effect of these supplements in relation to all-cause mortality, cardiovascular disease, cancer, or cognitive function [58]. In animal studies using mammalian models, many studies have shown that treatment with antioxidant supplements, when aimed at extending lifespan, result in no overt effect or even can have a negative effect [59]. ...
... In order to restore the oxidative balance, many antioxidant supplementation therapies (e.g., antioxidant vitamins, coenzyme Q, resveratrol, curcumin) have been implemented. However, tests of the effectiveness of such treatments in humans have raised contrasting results [199][200][201]. Some NRF2-activating compounds have been described as potential senotherapeutic drugs. ...
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The nuclear factor erythroid 2-related factor 2 (NRF2) was originally described as a master regulator of antioxidant cellular response, but in the time since, numerous important biological functions linked to cell survival, cellular detoxification, metabolism, autophagy, proteostasis, inflammation, immunity, and differentiation have been attributed to this pleiotropic transcription factor that regulates hundreds of genes. After 40 years of in-depth research and key discoveries, NRF2 is now at the center of a vast regulatory network, revealing NRF2 signalling as increasingly complex. It is widely recognized that reactive oxygen species (ROS) play a key role in human physiological and pathological processes such as ageing, obesity, diabetes, cancer, and neurodegenerative diseases. The high oxygen consumption associated with high levels of free iron and oxidizable unsaturated lipids make the brain particularly vulnerable to oxidative stress. A good stability of NRF2 activity is thus crucial to maintain the redox balance and therefore brain homeostasis. In this review, we have gathered recent data about the contribution of the NRF2 pathway in the healthy brain as well as during metabolic diseases, cancer, ageing, and ageing-related neurodegenerative diseases. We also discuss promising therapeutic strategies and the need for better understanding of cell-type-specific functions of NRF2 in these different fields.
... Antioxidant-rich diets have also been considered for a series of clinical trials with the goal of minimizing the elevated levels of oxidative stress that correlates with age. Unfortunately, many of these trials and experiments did not observe a positive effect with increasing dietary antioxidant supplements with regard to onset prevention or reducing symptoms of age-related diseases (Figure 3) (Sadowska-Bartosz and Bartosz, 2014;Conti et al., 2016;Gutteridge and Halliwell, 2018). In fact, administering large doses of antioxidant not only has demonstrated in many cases no therapeutic effect, but it has also been associated with worsening pathological outcomes in human subjects. ...
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The process of aging strongly correlates with maladaptive architectural, mechanical, and biochemical alterations that contribute to the decline in cardiac function. Consequently, aging is a major risk factor for the development of heart disease, the leading cause of death in the developed world. In this review, we will summarize the classic and recently uncovered pathological changes within the aged heart with an emphasis on the mitochondria. Specifically, we describe the metabolic changes that occur in the aging heart as well as the loss of mitochondrial fitness and function and how these factors contribute to the decline in cardiomyocyte number. In addition, we highlight recent pharmacological, genetic, or behavioral therapeutic intervention advancements that may alleviate age-related cardiac decline.
... Clinical trials with the supplementation of antioxidants did not prove beneficial in reducing ageing-associated disease or improving life expectancy. Further complicating the picture, it has been shown that the prolonged exposure to the exogenous antioxidants could have deleterious effects on the endogenous antioxidant systems, and some studies have shown that the long-term introduction of antioxidants in the diet actually reduced the overall lifespan [143,144]. ...
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The United States is undergoing a demographic shift towards an older population with profound economic, social, and healthcare implications. The number of Americans aged 65 and older will reach 80 million by 2040. The shift will be even more dramatic in the extremes of age, with a projected 400% increase in the population over 85 years old in the next two decades. Understanding the molecular and cellular mechanisms of ageing is crucial to reduce ageing-associated disease and to improve the quality of life for the elderly. In this review, we summarized the changes associated with the ageing of hematopoietic stem cells (HSCs) and what is known about some of the key underlying cellular and molecular pathways. We focus here on the effects of reactive oxygen species and the thioredoxin redox homeostasis system on ageing biology in HSCs and the HSC microenvironment. We present additional data from our lab demonstrating the key role of thioredoxin-1 in regulating HSC ageing.
... Administration of external antioxidant supplements (α-tocopherol, curcumin, vitamin-C, resveratrol, lipoic acid, coenzyme Q, melatonin, and other polyphenols) is extended longevity for bio-organisms, including Drosophila melanogaster and other flies. 74 Apart from life span expansion, antioxidants therapy prevented post-oxidative stress disorders such as Alzheimer's disease (AD), Multiple sclerosis, Parkinson's disease, depression, memory loss, etc. 75,76 Also, reports are available in the literature on early detection of oxidative stress biomarkers and controlling their overproduction. 72,77 Still, no report is available on the combination of lipoic acid with sesamol linked via chemical bond for longevity expansion in Drosophila melanogaster model. ...
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Phytonutrients, lipoic acid and sesamol, were chemically combined to yield medically important lipoic acid-sesamol conjugate (LSC). NMR and LC-MS/MS techniques were used to determine the chemical structure of LSC. The...
... Last, but not least, mitochondrial dihydrolipoyl dehydrogenase (DLD; EC 1.8.1.4) administrating alpha-lipoic acid is beneficial to a number of diseases caused by oxidative stress in animals [85,86], and regulates the lifespan and aging in yeasts [87] and pea seeds [77]. MetO-containing proteins identified in our study (Table 1) involved aldehyde oxidase and indole-3-acetaldehyde oxidase, two enzymes catalyzing the last step in the biosynthesis of two phytohormones, auxin and abscisic acid [88,89], both of which playing crucial roles in seed development and germination [8,[90][91][92]. ...
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In recent years, several reports pointed out the role of protein oxidation in seed longevity, notably regarding the oxidation of methionine (Met) residues to methionine sulfoxide (MetO) in proteins. To further consider this question, we present a handy proteomic method based on the use of two-dimensional diagonal electrophoresis (2Dd) and cyanogen bromide (CNBr) cleavage, which we refer to as 2Dd-CNBr. CNBr treatment of proteins causes the non-enzymatic hydrolysis of peptide bonds on the carboxyl side of reduced Met residues. However, Met oxidation causes a lack of cleavage, thus modifying the electrophoretic mobility of CNBr-induced peptides. This approach was first validated using bovine serum albumin as a model protein, which confirmed the possibility of distinguishing between oxidized and non-oxidized forms of Met-containing peptides in gels. Then, the 2Dd-CNBr method was applied to the Arabidopsis thaliana seed protein extract in a control (non-oxidized) condition and in an oxidized one (as obtained following hypochlorous acid treatment). Twenty-four oxidized Met residues in 19 proteins identified by mass spectrometry were found to be surface exposed in these proteins. In the three-dimensional environment of the oxidized Met, we detected amino acid residues that could be converted by oxidation (carbonylation) or by phosphorylation, suggesting a possible interplay between Met oxidation and the other protein modifications. The identification of the proteins oxidatively modified in Met residues revealed the finding that MetO-containing proteins are related to seed longevity. Based on these results, we suggest that the method presently described also has the potential for wider applications.