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OBM Geriatrics

(ISSN 2638-1311)

OBM Geriatrics is an international peer-reviewed Open Access journal published quarterly online by LIDSEN Publishing Inc. The journal takes the premise that innovative approaches – including gene therapy, cell therapy, and epigenetic modulation – will result in clinical interventions that alter the fundamental pathology and the clinical course of age-related human diseases. We will give strong preference to papers that emphasize an alteration (or a potential alteration) in the fundamental disease course of Alzheimer’s disease, vascular aging diseases, osteoarthritis, osteoporosis, skin aging, immune senescence, and other age-related diseases.

Geriatric medicine is now entering a unique point in history, where the focus will no longer be on palliative, ameliorative, or social aspects of care for age-related disease, but will be capable of stopping, preventing, and reversing major disease constellations that have heretofore been entirely resistant to interventions based on “small molecular” pharmacological approaches. With the changing emphasis from genetic to epigenetic understandings of pathology (including telomere biology), with the use of gene delivery systems (including viral delivery systems), and with the use of cell-based therapies (including stem cell therapies), a fatalistic view of age-related disease is no longer a reasonable clinical default nor an appropriate clinical research paradigm.

Precedence will be given to papers describing fundamental interventions, including interventions that affect cell senescence, patterns of gene expression, telomere biology, stem cell biology, and other innovative, 21st century interventions, especially if the focus is on clinical applications, ongoing clinical trials, or animal trials preparatory to phase 1 human clinical trials.

Papers must be clear and concise, but detailed data is strongly encouraged. The journal publishes a variety of article types (Original Research, Review, Communication, Opinion, Comment, Conference Report, Technical Note, Book Review, etc.). There is no restriction on the length of the papers and we encourage scientists to publish their results in as much detail as possible.

Publication Speed (median values for papers published in 2023): Submission to First Decision: 5.7 weeks; Submission to Acceptance: 17.9 weeks; Acceptance to Publication: 7 days (1-2 days of FREE language polishing included)

Current Issue: 2024  Archive: 2023 2022 2021 2020 2019 2018 2017
Open Access Review

Do Antioxidants Extend Longevity in Invertebrate and Vertebrate Animals?

Sami Badwan , Elizabeth Bailey , James M. Harper *

Department of Biological Sciences, Sam Houston State University, Huntsville, TX, USA

* Correspondence: James M. Harper

Academic Editor: Tamas Fulop

Received: November 09, 2022 | Accepted: March 02, 2023 | Published: March 07, 2023

OBM Geriatrics 2023, Volume 7, Issue 1, doi:10.21926/obm.geriatr.2301226

Recommended citation: Badwan S, Bailey E, Harper JM. Do Antioxidants Extend Longevity in Invertebrate and Vertebrate Animals? OBM Geriatrics 2023; 7(1): 226; doi:10.21926/obm.geriatr.2301226.

© 2023 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

Abstract

In the 1950’s Denham Harman proposed the Free Radical Theory of Aging whereby species lifespan and individual longevities are the consequence of free radical driven damage to biomolecules. This led to decades of research to ascertain the effect of altered antioxidant defense systems on aging and mortality in an array of species using reverse genetics and dietary manipulation. Within invertebrates, the data generally support the Free Radical Theory in that overexpression of antioxidant enzymes or dietary supplementation with antioxidant compounds increases longevity and resistance to oxidative damage. Likewise, genetic knockdown of antioxidant defenses generally shortens longevity within invertebrates. On the other hand, for endothermic vertebrates (i.e., birds and mammals) the results have been equivocal. Downregulation of antioxidant enzymes typically results in an increased oxidative burden, but without an appreciable effect on longevity, while dietary supplementation with antioxidants has little-to-no effect, at least at the concentrations used. Upregulation of antioxidant enzyme genes also fails to increase longevity in vertebrates most of the time. Interestingly, manipulating antioxidant defenses in fishes increases longevity in conjunction with reduced oxidative damage akin to what is seen in invertebrates. Since invertebrates and fishes are both exothermic this raises the possibility that the evolution of endothermy interferes with the ability of antioxidants to slow the aging process.

Keywords

Antioxidant; oxidative stress; longevity; eukaryotes

1. Introduction

Aging is an unavoidable, universal, phenomenon that impacts all organisms. Many hypotheses have been proposed to explain both cellular and molecular mechanisms of aging with the Free Radical Theory of Aging first suggested by Denham Harman being one of the most prevalent [1]. In short, it posits that aging is due to the accumulation of molecular damage downstream of free radicals and other reactive oxygen species (ROS) that are an inevitable consequence of metabolism and various exogenous sources [2] and has been cited as central to regulating human longevity [3,4].

Ultimately, oxidative stress is the consequence of an imbalance between the production of ROS in cells and tissues and the antioxidant mechanisms meant to combat them which leads to the accumulation of oxidative damage. As the name implies, ROS are highly reactive molecules that act as oxidizing agents in reduction-oxidation (i.e., redox) reactions and can damage nucleic acids (both DNA and RNA), proteins, and lipids. If enough damage accumulates, it can lead to cell death [5].

Organisms have evolved multiple endogenous antioxidant defenses, most notably antioxidant enzymes (e.g., catalase) that are responsible for the direct conversion of ROS to less damaging or inert molecules. In addition, there are endogenous substrates that are differentially oxidized or reduced when coupled with specific enzymes (e.g., glutathione and glutathione reductase). Finally, many substances found in foodstuffs or medicinal plants can serve as exogenous antioxidants, especially polyphenols and carotenoids [6]. Nutritional antioxidants act through various mechanisms but are mainly free radical scavengers that directly neutralize free radicals, reduce peroxide concentration, or quench iron to decrease ROS production [7].

Here, we will address whether there is evidence for antioxidants acting as a buffer against the aging process. This is not a new question [8,9] and we apologize to researchers whose work is not included, but the goal of this paper is to serve as a refresher about the uncertainty surrounding this topic, while providing an update on what has been learned during the past 10-plus years using additional models, rather than being a comprehensive review. Specifically, given the underlying assumption that mitigating the detrimental effects of ROS in intact organisms should extend longevity, the prevailing hypothesis is that an increase in antioxidant defense mechanisms coupled with reduced oxidative damage should extend longevity. The converse is that increased oxidative damage, regardless of cause, should reduce longevity. More recently, interest in the effect of various anti-aging strategies on the healthspan of an individual, defined as the time spent free from chronic illness and disabilities associated with aging, has increased but the relevance of extending healthspan, or even what it means, is still debated, and will not be addressed here [10].

1.1 Endogenous Antioxidants

Antioxidants can inhibit or delay the oxidation of a substrate when present [11] and are broadly divided into one of two classes: (1) enzymatic antioxidants and (2) non-enzymatic antioxidants. However, some non-enzymatic antioxidants require an enzyme to catalyze specific redox reactions central to their effects [11]. The role of enzymatic antioxidants is to directly remove free radical species from both the intracellular and extracellular compartments. This involves the conversion of a highly reactive molecule such as superoxide to a less reactive species (hydrogen peroxide). The less reactive species can then be rendered inert, for example via its conversion to water. This often occurs in the presence of cofactors such as copper, zinc, manganese, or iron [12]. In some cases, antioxidant enzymes work in tandem to convert hydroperoxides into non-radical, non-reactive thermally stable products [13].

Superoxide dismutases (SODs) are critical primary antioxidants found in both prokaryotes and eukaryotes thought to protect against senescence, and the accumulation of tissue damage due to lipid peroxidation and/or protein denaturation. Primary antioxidants such as SODs are the most potent defense mechanism against free radicals and harmful inflammatory reactions [13]. Cu-Zinc SOD is found predominantly in the cytoplasm and is responsible for the dismutation of superoxide radicals to form hydrogen peroxide (H2O2) [14] while Mn-SOD is found in the mitochondrial matrix and is crucial to detoxifying singlet oxygen radicals generated by mitochondrial respiration [15]. Although not relevant to mammals, Fe-SOD is typically found in prokaryotes and the chloroplast of some plants and is crucial in the conversion of superoxide to oxygen and hydrogen peroxide [16,17].

Although not as reactive as other ROS’s, H2O2 has the potential to cause significant damage if left unchecked [18,19]. More than likely, the antioxidant enzyme catalase (CAT) has the widest taxonomic distribution, having been described in all aerobic organisms and is responsible for catalyzing the detoxification of H2O2 to water and molecular oxygen. Glutathione peroxidase also reduces H2O2 and other peroxides and is part of a larger system involving glutathione reductase, glutathione-s-transferase and the protein glutathione. Glutathione is the most abundant antioxidant protein found in eukaryotic cells where it serves as a co-factor for glutathione peroxidase and glutathione reductase [5,13]. Glutathione can also directly react with free radicals to prevent damage to crucial cellular components [20]. For glutathione peroxidase to be able to reduce H2O2 it needs glutathione reductase to maintain a pool of cysteine-thiol groups in a reduced state [21]. Meanwhile, glutathione-s-transferases are involved with the direct detoxification of xenobiotics and the reduction of lipid peroxides due to glutathione peroxidase activity [20]. Finally, the thioredoxin (Trx) system serves as an antioxidant defense mechanism in vertebrates via the maintenance of a reducing environment. This is accomplished by catalyzing electron flux from nicotinamide adenine dinucleotide phosphate (NADP+) through thioredoxin reductase which reduces target proteins by utilizing conserved thiols [22]. See Figure 1 for an overview of these processes. In humans, two forms of thioredoxin have been identified which are in the cytosol (Trx1) and mitochondria (Trx2), respectively [23].

Click to view original image

Figure 1 The glutathione and thioredoxin systems. 1) Glutathione serves as a substrate for glutathione reductase, glutathione peroxidase and glutathione-s-transferase. Glutathione peroxidase activity reduces hydrogen peroxide to water to mitigate against its damaging effect; glutathione reductase catalyzes the reduction of oxidized glutathione to regenerate the supply of reduced glutathione using nicotinamide adenine dinucleotide phosphate (NADPH) as a reducing factor; glutathione-s-transferase uses reduced glutathione for detoxification via conjugation to xenobiotic compounds. 2) In the thioredoxin system, thioredoxin reductase is used to deliver reducing equivalents from NADPH to thioredoxin with reduced thioredoxin being used catalyze the reduction of disulfides within oxidized proteins.

1.2 Exogenous Antioxidants

Non-enzymatic antioxidants act by quenching free radicals directly or indirectly via the promotion of other processes necessary for radical scavenging [13] to prevent reactive species from being formed or to remove them before harmful damage can occur [24]. Non-enzymatic antioxidants are comprised mostly of nutrients such as vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), N-acetyl cysteine and carotenoids [12,25].

Vitamin C is a water-soluble antioxidant found in both the intracellular and extracellular compartments where it directly scavenges oxygen free radicals in aqueous environments and defends against the oxidation of cholesterols [26]. Vitamin C also assists with converting vitamin E from its oxidized to its reduced form [18]. Foodstuffs with an abundance of vitamin C include fruits, vegetables, beef, cereals, poultry, and fish [13]. Meanwhile, Vitamin E is a lipid soluble antioxidant present in the cell membrane and is a component of lipoproteins where it serves to inhibit lipid peroxidation. Vitamin E is abundant in vegetable oils, mangoes, almonds and other nuts, and broccoli [27]. The lipid soluble precursor for vitamin A synthesis, β-carotene, can function synergistically with vitamin E to protect against lipid peroxidation [13]. N-acetyl cysteine (NAC) is used for glutathione synthesis, but since it contains a thiol group, NAC can donate electrons for the detoxification of ROS and the protection of sulfhydryl-containing proteins from oxidative damage [28]. Typically, NAC levels are maintained via the consumption of cysteine, which is found in high protein foods [29]. Carotenoids are pigments that play a key role in protecting plants against photo-oxidative processes and are efficient antioxidants that scavenge singlet molecular oxygen and peroxyl radicals [30]. In humans, carotenoids are part of the antioxidant defense system and work synergistically with other antioxidants [30].

The tenets of the Free Radical Theory of aging implicate ROS, and the induction of oxidative stress, as a causal agent in the aging process. Hence, interventions to reduce oxidative stress should slow aging and increase species’ lifespan. Although they are often used interchangeably, lifespan and longevity are not equivalent. Specifically, there are differences in lifespans among species, while differences in longevity occur among individuals of the same species. This is important because a species’ lifespan is the consequence of evolution and its effect on a suite of parameters that contribute to the unique physiology of an individual species. Differences in longevity among individuals of the same species, meanwhile, are the consequence of an individual’s unique allelic composition and how it shapes its response to exogenous inputs.

1.3 Impact of Enzymatic and Non-enzymatic Antioxidants on Vertebrate Longevity

Among vertebrates, there is little evidence to suggest that antioxidant defenses are correlated with differences in lifespan or longevity. For example, in a study of antioxidant enzyme activity in heart, brain and liver of 14 mammalian and avian species, only Mn-SOD and catalase demonstrated a significant relationship with lifespan, while there was no relationship for Cu-Zinc SOD, glutathione peroxidase, or glutathione reductase activity [31]. No appreciable difference in Mn-SOD, catalase, and glutathione peroxidase activity in tissues from mice relative to naked mole rats, an extremely long-lived rodent model of aging, has also been reported [32]. Data from dermal fibroblasts collected from several mammalian species gave parallel results to whole organ lysates [33], while a negative relationship between species lifespan and antioxidant activity of lung has been reported [34]. In birds, there is some evidence for increased antioxidant capacity and long-life among species [35], but maybe only for specific antioxidant defenses [36]. Within fishes there is a positive relationship between antioxidant activity in in some, but not all, organs [37].

At the individual species level, within mice overexpression of Cu-Zinc SOD had no effect on longevity [38]. This finding has been repeatedly demonstrated in other rodent models [38,39]. In the case of thioredoxin and thioredoxin reductase, a negative relationship between their activity and species lifespan was observed in both mammals and birds [40,41]. Genetic manipulation of Trx1 and Trx2 in C57BL/6 mice did increase their resistance to oxidative stress and reduced the degree of oxidative damage, but there was a statistically insignificant effect on longevity [23,42]. Interestingly, while genetic knockout of antioxidant enzyme genes can reduce longevity in vertebrate models [43,44,45,46,47,48] there are many notable exceptions even in the presence of increased oxidative damage. This has been shown most robustly in genetically modified mice [39,42,49,50,51], but more recent studies using short-lived fish have also shown no correlation between the degree of oxidative stress and mortality [52]. An important caveat for these studies is that the genetic manipulations used typically only result in a single change in the “dose” of the gene being tested. That is, the dosage is altered to a specific degree because of the manipulation that was used. For example, expression may be increased or decreased by 50%, but the degree to which it changes varies from one study to the next. Typically, a range of differences in the degree of “dosing” within the same population is not generated and so it is possible that the ideal “dose” has been missed. The expression system used may also influence the outcome [53].

Dietary supplementation of antioxidants has also failed to demonstrate a convincing positive effect on species longevity. For example, NAC supplementation in mice did significantly increase longevity in male mice, but there was no effect in females [54]. However, the increase in male longevity may actually be the consequence of reduced food intake (i.e., dietary restriction) rather than a direct effect of NAC itself. Meanwhile, Vitamin E supplementation has given mixed effects in that several studies have failed to show an increase in longevity in mice [55,56,57,58,59,60], while others reported a significant increase in longevity even in the absence of a demonstrable effect on oxidative damage [61]. Vitamin C supplementation has also been reported to increase longevity in mice, but similar to NAC supplementation this effect may be secondary to reduced food intake [62]. Mice fed a mixture of antioxidants showed an increase in longevity if the supplementation began early in life, but the appreciable variation in the median longevity among the controls (i.e., in the absence of antioxidant supplementation) makes the significance of this finding uncertain [63] while other studies demonstrating a diet-induced increase in antioxidant gene expression did not increase longevity in mice [48,64]. Finally, a mitochondrial targeted antioxidant supplement found that housing condition was an important modulator of the effect on longevity [65].

The lack of a consistent and/or convincing effect of dietary antioxidant supplementation on longevity extends to species other than mice. For example, Selman et al. [60] fed a diet containing either Vitamin C or Vitamin E to a species of vole and found that longevity was significantly decreased. Vitamin C supplementation in guinea pigs also showed no beneficial effect [66] and human trials have largely failed to show a beneficial effect of dietary antioxidants as well, including vitamin C, vitamin E, vitamin A, and β-carotene. And similar to voles, the risk of mortality was actually increased when antioxidant supplements were provided to humans in some cases [25,67]. Taken together, these inconsistent results have led to the speculation that there may be a beneficial effect of dietary antioxidants that is a consequence of something other than their antioxidant properties, such as altered tumor growth [59]. Not surprisingly, species identity has been implicated as well, with a krill oil supplemented diet shortening the longevity of mice while increasing the longevity of an annual fish (Nothobranchius guentheri) that has become an increasingly popular model for vertebrate aging research [68]. Indeed, longevity in N. guentheri and another fish species (medaka, Oryzias latipes) is increased in conjunction with a reduction in markers of oxidative stress when fed dietary supplements [69,70]. As with gene dosage, it is possible the proper dose of antioxidant supplementation has not been achieved for a given species and/or the feeding duration itself was insufficient (or too long) [68]. The findings for antioxidant manipulation in vertebrates is summarized in Table 1.

Table 1 Effect of antioxidants on vertebrate longevity.

1.4 Impact of Enzymatic and Non-enzymatic Antioxidants on Invertebrate Longevity

Due to the relative ease of use and rapid turnaround time, genetically modified invertebrate models were the most heavily used early in the investigation of antioxidant defense genes and lifespan regulation. Overall, these works generated a strong body of evidence suggesting enhanced antioxidant defenses have a significant positive effect on invertebrate lifespan and/or longevity with yeast (Saccharomyces spp.), fruit flies (Drosophila melanogaster) and the nematode worm Caenorhabditis elegans being the best studied. This contrasts with the mixed results obtained from vertebrate models reviewed above.

For example, overexpression of superoxide dismutases increases chronological (but not replicative) longevity in yeast [71], as well as D. melanogaster and C. elegans [72,73,74,75], although the increase in longevity did not coincide with a decrease in oxidative damage in C. elegans. In fact, protein oxidation was increased in this model leading the authors to speculate that overexpression of superoxide dismutase resulted in changes in longevity-promoting transcriptional activity, rather than an antioxidant effect per se [76,77]. Increased SOD gene activity has also been reported to be necessary for longevity-assurance in a long-lived mutant strain of C. elegans [78]. Interestingly, SOD mutants with reduced enzyme activity display a marked increase in oxidative damage but have a normal longevity [79] that is partially dependent on the cellular location that a specific isoform is normally expressed, for example in the mitochondria versus the cytosol [79,80,81].

On the other hand, Orr and Sohal [82] reported increased longevity in fruit flies overexpressing SOD that was associated with reduced protein oxidation and that the loss of SOD activity significantly reduced longevity. Another study also reported a positive effect on longevity when SOD is overexpressed, but it was not statistically significant [83]. Interestingly, there is no beneficial effect of catalase overexpression on longevity in D. melanogaster despite an increased resistance to hydrogen peroxide induced toxicity [72,84], while RNAi-mediated reduction in catalase activity shortens the longevity of both sand flies (Lutzomyia longipalpis) and D. melanogaster [85,86]. This is true for RNAi-mediated downregulation of SOD in D. melanogaster as well [86], but longevity is unaffected in an SOD hypomorph [87].

Other enzymatic antioxidants that extend longevity in invertebrates when overexpressed include thioredoxin in both D. melanogaster and C. elegans [78,88,89]. In budding yeast, increased peroxiredoxin activity increases replicative lifespan via scavenging peroxide and due to its chaperone activity [90]. Tissue-specific overexpression peroxiredoxin in the neurons of D. melanogaster also increased longevity when expressed in the cytoplasm of the endoplasmic reticulum alone [91,92]. Meanwhile, reduced glutathione peroxidase activity in C. elegans shortens longevity [93] but reduced peroxiredoxin activity has no effect [94].

As with vertebrates, there has been a long-standing interest in screening dietary supplements for their anti-aging properties using invertebrate models [95]. Indeed, dietary supplementation using well-known antioxidants (e.g., Vitamins C and E) increases longevity under varying conditions, and in varied genetic backgrounds, in fruit flies [96] while Vitamin C supplementation increases longevity in yeast and C. elegans [97,98]. As is often the case, too much Vitamin C is toxic, however [96]. This parabolic relationship between dose and longevity is also observed with N-acetylcysteine (NAC) supplementation. For example, C. elegans and Drosophila spp. given a low dose of NAC have significantly increased longevity, while a high dose is detrimental [99,100]. In the case of Vitamin E supplementation, it is more complicated. In budding yeast, Vitamin E reduces replicative lifespan [101], but increases longevity in C. elegans despite no effect on the degree of superoxide damage [102,103]. In D. melanogaster, the specific form of Vitamin E used was important, as well as the dose at which it was administered [55,104]. Carotenoid supplementation has not been well-studied, but it does prolong longevity in the mealworm beetle (Tenebrio molito), but most likely due to its effects on immune function and not oxidative stress [105]. In both D. melanogaster and C. elegans, carotenoid supplementation does increase longevity [106,107,108].

In addition to these more traditional antioxidants, multiple studies have demonstrated a beneficial effect (i.e., increased survival) of various supplements that act either directly as antioxidants or that induce antioxidant activity in invertebrate models. Many of these compounds are derived from plants, such as hawthorn [109] and canary seed [110] or from fungi, such as shitake mushroom [111], but also include synthetic drugs [112]. While most of these studies have been conducted in C. elegans, similar findings have been seen with plant extracts in D. melanogaster [113,114,115], yeast [116,117] and rotifers [118]. The findings for antioxidant manipulation in invertebrates are summarized in Table 2.

Table 2 Effect of antioxidants on invertebrate longevity.

2. Conclusions

Within invertebrate models, genetic manipulation of endogenous antioxidant defenses has the expected outcome on longevity, be it increased or decreased dependent on the situation, while supplementation with various exogenous antioxidant compounds has a beneficial effect in most cases. Not unexpectedly, there are exceptions to these findings due to a variety of mitigating factors, such as species, strain, specific manipulation (including dosing), et cetera, but the consensus seems to be that oxidative stress and longevity are strongly correlated within invertebrates. Within vertebrates, however, the conclusions are muddled. A little over 10 years ago, the Free Radical Theory of Aging was called into question based largely on the lack of a tangible effect of genetic models of impaired oxidative stress resistance on longevity within mice, as well as inconclusive findings using dietary supplementation with various antioxidant compounds [8,9]. Since that time, additional studies in various vertebrate models, using different experimental approaches, has done little to change this notion, perhaps except for increased oxidative stress consistently reducing longevity in fishes. However, fishes are exotherms, just as invertebrates are, but mice (i.e., mammals) are endotherms. So too are birds, which also fail to show a consistent effect of oxidative stress and/or antioxidant capacity on the aging process [119]. Taken together, this suggests that the relevance of oxidative stress as a potential modulator of the aging process in humans is minimal, although it certainly is involved in numerous pathophysiological processes.

Acknowledgments

We would like to thank the Department of Biological Sciences and the Office of Research and Sponsored Programs at Sam Houston State University for valuable feedback during the writing process.

Author Contributions

SB and EB wrote and edited the manuscript with support from JMH. JMH conceived the framework and direction of the manuscript.

Funding

Funding was provided from the Department of Biological Sciences and the Office of Research and Sponsored Programs at Sam Houston State University.

Competing Interests

The authors have declared that no competing interests exist.

References

  1. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol. 1956; 11: 298-300. [CrossRef]
  2. Sadowska-Bartosz I, Bartosz G. Effect of antioxidants supplementation on aging and longevity. BioMed Res Int. 2014; 2014: 404680. [CrossRef]
  3. Martemucci G, Portincasa P, Di Ciaula A, Mariano M, Centonze V, D’Alessandro AG. Oxidative stress, aging, antioxidant supplementation and their impact on human health: An overview. Mech Ageing Dev. 2022; 206: 111707. [CrossRef]
  4. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev. 2017; 2017: 8416763. [CrossRef]
  5. Poljsak B, Šuput D, Milisav I. Achieving the balance between ROS and antioxidants: When to use the synthetic antioxidants. Oxid Med Cell Longev. 2013; 2013: 956792. [CrossRef]
  6. Xu DP, Li Y, Meng X, Zhou T, Zhou Y, Zheng J, et al. Natural antioxidants in foods and medicinal plants: Extraction, assessment and resources. Int J Mol Sci. 2017; 18: 96. [CrossRef]
  7. Berger MM. Can oxidative damage be treated nutritionally? Clin Nutr. 2005; 24: 172-183. [CrossRef]
  8. Salmon AB, Richardson A, Pérez VI. Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging? Free Radic Biol Med. 2010; 48: 642-655. [CrossRef]
  9. Speakman JR, Selman, C. The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan. BioEssays. 2011; 33: 255-259. [CrossRef]
  10. Kaeberlein M. How healthy is the healthspan concept? GeroScience. 2018; 40: 361-364. [CrossRef]
  11. Fusco D, Colloca G, Lo Monaco MR, Cesari M. Effects of antioxidant supplementation on the aging process. Clin Interv Aging. 2007; 2: 377-387.
  12. Nimse SB, Pal D. Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv. 2015; 5: 27986-28006. [CrossRef]
  13. Rasheed A, Azeez RF. A review on natural antioxidants. In: Traditional and complementary medicine. London: IntechOpen; 2019. [CrossRef]
  14. Lustgarten MS, Jang YC, Liu Y, Qi W, Qin Y, Dahia PL, et al. MnSOD deficiency results in elevated oxidative stress and decreased mitochondrial function but does not lead to muscle atrophy during aging. Aging Cell. 2011; 10: 493-505. [CrossRef]
  15. Candas D, Li JJ. MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx. Antiox Redox Signal. 2014; 20: 1599-1617. [CrossRef]
  16. Cakmak I, Horst WJ. Effect of aluminum on lipid peroxidation, superoxide dismutase, catalase, and peroxidase activities in root tips of soybean (Glycine max). Physiol Plant. 1991; 83: 463-468. [CrossRef]
  17. Wang Y, Branicky R, Noë A, Hekimi, S. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 2018; 217: 1915-1928. [CrossRef]
  18. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012; 5: 9-19. [CrossRef]
  19. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2019; 54: 287-293. [CrossRef]
  20. Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, et al. Oxidative stress, prooxidants, and antioxidants: The interplay. BioMed Res Int. 2014; 2014: 761264. [CrossRef]
  21. Chen SX, Schopfer P. Hydroxyl-radical production in physiological reactions. A novel function of peroxidase. Eur J Biochem. 1999; 260: 726-735. [CrossRef]
  22. Lee S, Kim SM, Lee RT. Thioredoxin and thioredoxin target proteins: From molecular mechanisms to functional significance. Antiox Redox Signal. 2013; 18: 1165-1207. [CrossRef]
  23. Roman MG, Flores LC, Cunningham GM, Cheng C, Allen C, Hubbard GB, et al. Thioredoxin and aging: What have we learned from the survival studies? Aging Pathobiol Ther. 2020; 2: 126-133. [CrossRef]
  24. Hatwalne MS. Free radical scavengers in anesthesiology and critical care. Ind J Anesth. 2012; 56: 227-233. [CrossRef]
  25. Shields HJ, Traa A, Van Raamsdonk JM. Beneficial and detrimental effects of reactive oxygen species on lifespan: A comprehensive review of comparative and experimental studies. Front Cell Dev Biol. 2021; 9: 628157. [CrossRef]
  26. Frei B. Reactive oxygen species and antioxidant vitamins: Mechanisms of action. Am J Med. 1994; 97: 5S-28S. [CrossRef]
  27. Herrera E, Barbas C. Vitamin E: Action, metabolism and perspectives. J Physiol Biochem. 2001; 57: 43-56. [CrossRef]
  28. Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, et al. N-acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radic Res. 2018; 52: 751-762. [CrossRef]
  29. Šalamon Š, Kramar B, Marolt TP, Poljšak B, Milisav I. Medical and dietary uses of N-acetylcysteine. Antioxidants. 2019; 8: 111. [CrossRef]
  30. Stahl W, Sies H. Antioxidant activity of carotenoids. Mol Aspects Med. 2003; 24: 345-351. [CrossRef]
  31. Page MM, Richardson J, Wiens BE, Tiedtke E, Peters CW, Faure PA, et al. Antioxidant enzyme activities are not broadly correlated with longevity in 14 vertebrate endotherm species. Age. 2010; 32: 255-270. [CrossRef]
  32. Andziak B, O'Connor TP, Qi W, DeWaal EM, Pierce A, Chaudhuri AR, et al. High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell. 2006; 5: 463-471. [CrossRef]
  33. Brown MF, Stuart, JA. Correlation of mitochondrial superoxide dismutase and DNA polymerase beta in mammalian dermal fibroblasts with species maximal lifespan. Mech Ageing Dev. 2007; 128: 696-705. [CrossRef]
  34. Pérez-Campo R, López-Torres M, Rojas C, Cadenas S, Barja R. Longevity and antioxidant enzymes, non-enzymatic antioxidants and oxidative stress in the vertebrate lung: A comparative study. J Comp Physiol B. 1994; 163: 682-689. [CrossRef]
  35. Galván I, Erritzøe J, Karadaş F, Møller AP. High levels of liver antioxidants are associated with life-history strategies characteristic of slow growth and high survival rates in birds. J Comp Physiol B. 2012; 182: 947-959. [CrossRef]
  36. Montgomery MK, Hulbert AJ, Buttemer WA. Does the oxidative stress theory of aging explain longevity differences in birds? I. Mitochondrial ROS production. Exp Gerontol. 2012; 47: 203-210. [CrossRef]
  37. Sanz A, Trenzado CE, Botello Castro H, López-Rodríguez MJ, Tierno de Figueroa JM. Relationship between brain and liver oxidative state and maximum lifespan potential of different fish species. Comp Biochem Physiol Part A Mol Integr Physiol. 2013; 165: 358-364. [CrossRef]
  38. Huang TT, Carlson EJ, Gillespie AM, Shi Y, Epstein CJ. Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. J Gerontol Biol Sci Med Sci. 2000; 55: B5-B9. [CrossRef]
  39. Pérez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, et al. Is the oxidative stress theory of aging dead? Biochim Biophys Acta Gen Subj. 2009; 1790: 1005-1014. [CrossRef]
  40. Pamplona R, Costantini D. Molecular and structural antioxidant defenses against oxidative stress in animals. Am J Physiol Regul Integr Comp Physiol. 2011; 301: R843-R863. [CrossRef]
  41. Salway KD, Page MM, Faure PA, Burness G, Stuart JA. Enhanced protein repair and recycling are not correlated with longevity in 15 vertebrate endotherm species. Age. 2010; 33: 33-47. [CrossRef]
  42. Pérez VI, Cortez LA, Lew CM, Rodriguez M, Webb CR, Van Remmen H, et al. Thioredoxin 1 overexpression extends mainly the earlier part of life span in mice. J Gerontol Biol Sci Med Sci. 2011; 66: 1286-1299. [CrossRef]
  43. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet. 1995; 11: 376-381. [CrossRef]
  44. Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, et al. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene. 2005; 24: 367-380. [CrossRef]
  45. Muller FL, Song W, Liu Y, Chaudhuri A, Pieke-Dahl S, Strong R, et al. Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy. Free Radic Biol Med. 2006; 40: 1993-2004. [CrossRef]
  46. Treiber N, Maity P, Singh K, Kohn M, Keist AF, Ferchiu F, et al. Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue. Aging Cell. 2011; 10: 239-254. [CrossRef]
  47. Pérez-Estrada JR, Hernández-García D, Leyva-Castro F, Ramos-León J, Cuevas-Benítez O, Díaz-Muñoz M, et al. Reduced lifespan of mice lacking catalase correlates with altered lipid metabolism without oxidative damage or premature aging. Free Radic Biol Med. 2019; 135: 102-115. [CrossRef]
  48. Borrás C, Abdelaziz KM, Díaz A, Gambini J, Jové M, López-Grueso R, et al. Lifelong soya consumption in males does not increase lifespan but increases health span under a metabolic stress such as type 2 diabetes mellitus. Mech Ageing Dev. 2021; 200: 111596. [CrossRef]
  49. Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, et al. Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics. 2003; 16: 29-37. [CrossRef]
  50. Jang YC, Pérez VI, Song W, Lustgarten MS, Salmon AB, Mele J, et al. Overexpression of Mn superoxide dismutase does not increase life span in mice. J Gerontol Biol Sci Med Sci. 2009; 64: 1114-1125. [CrossRef]
  51. Salmon AB, Kim G, Liu C, Wren JD, Georgescu C, Richardson A, et al. Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice. Redox Biol. 2016; 10: 251-256. [CrossRef]
  52. Godoy RS, Lanés L, Castro BD, Weber V, Wingen N, Pires MM, et al. Oxidative stress resistance in a short-lived Neotropical annual killifish. Biogerontology. 2020; 21: 217-229. [CrossRef]
  53. Adamson AD, Jackson D, Davis JR. Novel approaches to in vitro transgenesis. J Endocrinol. 2011; 208: 193-206. [CrossRef]
  54. Flurkey K, Astle CM, Harrison DE. Life extension by diet restriction and N-acetyl-L-cysteine in genetically heterogeneous mice. J Gerontol Biol Sci Med Sci. 2010; 65: 1275-1284. [CrossRef]
  55. Lipman RD, Bronson RT, Wu D, Smith DE, Prior R, Cao G, et al. Disease incidence and longevity are unaltered by dietary antioxidant supplementation initiated during middle age in C57BL/6 mice. Mech Ageing Dev. 1998; 103: 269-284. [CrossRef]
  56. Morley AA, Trainor KJ. Lack of an effect of vitamin E on lifespan of mice. Biogerontology. 2021; 2: 109-112. [CrossRef]
  57. Sumien N, Forster MJ, Sohal RS. Supplementation with vitamin E fails to attenuate oxidative damage in aged mice. Exp Gerontol. 2003; 38: 699-704. [CrossRef]
  58. Selman C, McLaren JS, Mayer C, Duncan JS, Collins AR, Duthie GG, et al. Lifelong alpha-tocopherol supplementation increases the median life span of C57BL/6 mice in the cold but has only minor effects on oxidative damage. Rejuvenation Res. 2008; 11: 83-96. [CrossRef]
  59. Banks R, Speakman JR, Selman C. Vitamin E supplementation and mammalian lifespan. Mol Nutr Food Res. 2010; 54: 719-725. [CrossRef]
  60. Selman C, McLaren JS, Collins AR, Duthie GG, Speakman JR. Deleterious consequences of antioxidant supplementation on lifespan in a wild-derived mammal. Biol Lett. 2013; 9: 20130432. [CrossRef]
  61. Navarro A, Gómez C, Sánchez-Pino MJ, González H, Bández MJ, Boveris AD, et al. Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. Am J Physiol Regul Integr Comp Physiol. 2005; 289: R1392-R1399. [CrossRef]
  62. Massie HR, Aiello VR, Doherty TJ. Dietary vitamin C improves the survival of mice. Gerontology. 1984; 30: 371-375. [CrossRef]
  63. Bezlepkin VG, Sirota NP, Gaziev AI. The prolongation of survival in mice by dietary antioxidants depends on their age by the start of feeding this diet. Mech Ageing Dev. 1996; 92: 227-234. [CrossRef]
  64. Wang Z, Komatsu T, Ohata Y, Watanabe Y, Yuan Y, Yoshii Y, et al. Effects of rikkunshito supplementation on resistance to oxidative stress and lifespan in mice. Geriatr Gerontol Int. 2020; 20: 238-247. [CrossRef]
  65. Anisimov VN, Egorov MV, Krasilshchikova MS, Lyamzaev KG, Manskikh VN, Moshkin MP, et al. Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents. Aging. 2011; 3: 1110-1119. [CrossRef]
  66. Davies JE, Hughes RE. A note on the effect of food restriction on tissue ascorbic acid in guinea-pigs. Br J Nutr. 1977; 38: 299-300. [CrossRef]
  67. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2012. Doi: 10.1002/14651858.CD007176.pub2. [CrossRef]
  68. Song L, Leng K, Xiao K, Zhang S. Administration of krill oil extends lifespan of fish Nothobranchius guentheri via enhancement of antioxidant system and suppression of NF-κB pathway. Fish Physiol Biochem. 2022; 48: 1057-1073. [CrossRef]
  69. Sánchez-Sánchez AV, Leal-Tassias A, Rodríguez-Sánchez N, Piquer-Gil M, Martorell P, Genovés S, et al. Use of medaka fish as vertebrate model to study the effect of cocoa polyphenols in the resistance to oxidative stress and life span extension. Rejuvenation Res. 2018; 21: 323-332. [CrossRef]
  70. Song L, Zhou Y, Ni S, Wang X, Yuan J, Zhang Y, et al. Dietary intake of β-glucans can prolong lifespan and exert an antioxidant action on aged fish nothobranchius guentheri. Rejuvenation Res. 2020; 23: 293-301. [CrossRef]
  71. Harris N, Costa V, MacLean M, Mollapour M, Moradas-Ferreira P, Piper PW. MnSod overexpression extends the yeast chronological (G(0)) life span but acts independently of Sir2p histone deacetylase to shorten the replicative life span of dividing cells. Free Radic Biol Med. 2003; 34: 1599-1606. [CrossRef]
  72. Sun J, Tower J. FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol Cell Biol. 1999; 19: 216-228. [CrossRef]
  73. Sun J, Folk D, Bradley TJ, Tower J. Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics. 2002; 161: 661-672. [CrossRef]
  74. Sun J, Molitor J, Tower J. Effects of simultaneous over-expression of Cu/ZnSOD and MnSOD on Drosophila melanogaster life span. Mech Ageing Dev. 2004; 125: 341-349. [CrossRef]
  75. Curtis C, Landis GN, Folk D, Wehr NB, Hoe N, Waskar M, et al. Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes. Genome Biol. 2007; 8: R262. [CrossRef]
  76. Honda Y, Honda S. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 1999; 13: 1385-1393. [CrossRef]
  77. Cabreiro F, Ackerman D, Doonan R, Araiz C, Back P, Papp D, et al. Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med. 2011; 51: 1575-1582. [CrossRef]
  78. Harris-Gauthier N, Traa A, Al Okda A, Moldakozhayev A, Anglas U, Soo SK, et al. Mitochondrial thioredoxin system is required for enhanced stress resistance and extended longevity in long-lived mitochondrial mutants. Redox Biol. 2022; 53: 102335. [CrossRef]
  79. Van Raamsdonk JM, Hekimi S. Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci U S A. 2012; 109: 5785-5790. [CrossRef]
  80. Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, et al. Against the oxidative damage theory of aging: Superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev. 2008; 22: 3236-3241. [CrossRef]
  81. Yanase S, Onodera A, Tedesco P, Johnson TE, Ishii N. SOD-1 deletions in Caenorhabditis elegans alter the localization of intracellular reactive oxygen species and show molecular compensation. J Gerontol Biol Sci Med Sci. 2009; 64: 530-539. [CrossRef]
  82. Orr WC, Sohal RS. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science. 1994; 263: 1128-1130. [CrossRef]
  83. Seto NO, Hayashi S, Tener GM. Overexpression of Cu-Zn superoxide dismutase in Drosophila does not affect life-span. Proc Natl Acad Sci U S A. 1990; 87: 4270-4274. [CrossRef]
  84. Orr WC, Sohal RS. The effects of catalase gene overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys. 1992; 297: 35-41. [CrossRef]
  85. Diaz-Albiter H, Mitford R, Genta FA, Sant'Anna MR, Dillon RJ. Reactive oxygen species scavenging by catalase is important for female Lutzomyia longipalpis fecundity and mortality. PloS One. 2011; 6: e17486. [CrossRef]
  86. Deepashree S, Shivanandappa T, Ramesh SR. Genetic repression of the antioxidant enzymes reduces the lifespan in Drosophila melanogaster. J Comp Physiol B. 2022; 192: 1-13. [CrossRef]
  87. Blackney MJ, Cox R, Shepherd D, Parker JD. Cloning and expression analysis of Drosophila extracellular Cu Zn superoxide dismutase. Biosci Rep. 2014; 34: e00164. [CrossRef]
  88. Miranda-Vizuete A, Fierro González JC, Gahmon G, Burghoorn J, Navas P, Swoboda P. Lifespan decrease in a Caenorhabditis elegans mutant lacking TRX-1, a thioredoxin expressed in ASJ sensory neurons. FEBS Lett. 2006; 580: 484-490. [CrossRef]
  89. Umeda-Kameyama Y, Tsuda M, Ohkura C, Matsuo T, Namba Y, Ohuchi Y, et al. Thioredoxin suppresses Parkin-associated endothelin receptor-like receptor-induced neurotoxicity and extends longevity in Drosophila. J Biol Chem. 2007; 282: 11180-11187. [CrossRef]
  90. Roger F, Picazo C, Reiter W, Libiad M, Asami C, Hanzén S, et al. Peroxiredoxin promotes longevity and H2O2-resistance in yeast through redox-modulation of protein kinase A. Elife. 2020; 9: e60346. [CrossRef]
  91. Lee KS, Iijima-Ando K, Iijima K, Lee WJ, Lee JH, Yu K, et al. JNK/FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span. J Biol Chem. 2009; 284: 29454-29461. [CrossRef]
  92. Klichko VI, Orr WC, Radyuk SN. The role of peroxiredoxin 4 in inflammatory response and aging. Biochim Biophys Acta Mol Basis Dis. 2016; 1862: 265-273. [CrossRef]
  93. Sakamoto T, Maebayashi K, Nakagawa Y, Imai H. Deletion of the four phospholipid hydroperoxide glutathione peroxidase genes accelerates aging in Caenorhabditis elegans. Genes Cells. 2014; 19: 778-792. [CrossRef]
  94. Ranjan M, Gruber J, Ng LF, Halliwell B. Repression of the mitochondrial peroxiredoxin antioxidant system does not shorten life span but causes reduced fitness in Caenorhabditis elegans. Free Radic Biol Med. 2013; 63: 381-389. [CrossRef]
  95. Martel J, Wu CY, Peng HH, Ko YF, Yang HC, Young JD, et al. Plant and fungal products that extend lifespan in Caenorhabditis elegans. Microb Cell. 2020; 7: 255-269. [CrossRef]
  96. Bahadorani S, Bahadorani P, Phillips JP, Hilliker AJ. The effects of vitamin supplementation on Drosophila life span under normoxia and under oxidative stress. J Gerontol Biol Sci Med Sci. 2008; 63: 35-42. [CrossRef]
  97. Desjardins D, Cacho-Valadez B, Liu JL, Wang Y, Yee C, Bernard K, et al. Antioxidants reveal an inverted U-shaped dose-response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans. Aging Cell. 2017; 16: 104-112. [CrossRef]
  98. Owsiak A, Bartosz G, Bilinski T. Oxidative stress during aging of the yeast in a stationary culture and its attenuation by antioxidants. Cell Biol Int. 2010; 34: 731-736. [CrossRef]
  99. Oh SI, Park JK, Park, SK. Lifespan extension and increased resistance to environmental stressors by N-acetyl-L-cysteine in Caenorhabditis elegans. Clinics. 2015; 70: 380-386. [CrossRef]
  100. Shaposhnikov MV, Zemskaya NV, Koval LA, Schegoleva EV, Zhavoronkov A, Moskalev AA. Effects of N-acetyl-L-cysteine on lifespan, locomotor activity and stress-resistance of 3 Drosophila species with different lifespans. Aging. 2018; 2428-2458. [CrossRef]
  101. Lam YT, Stocker R, Dawes IW. The lipophilic antioxidants alpha-tocopherol and coenzyme Q10 reduce the replicative lifespan of Saccharomyces cerevisiae. Free Radic Biol Med. 2010; 49: 237-244. [CrossRef]
  102. Harrington LA, Harley CB. Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech Ageing Dev. 1998; 43: 71-78. [CrossRef]
  103. Ishii N, Senoo-Matsuda N, Miyake K, Yasuda K, Ishii T, Hartman PS, et al. Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress. Mech Ageing Dev. 2003; 125: 41-46. [CrossRef]
  104. Driver C, Georgeou A. Variable effects of vitamin E on Drosophila longevity. Biogerontology. 2003; 4: 91-95. [CrossRef]
  105. Dhinaut J, Balourdet A, Teixeira M, Chogne M, Moret Y. A dietary carotenoid reduces immunopathology and enhances longevity through an immune depressive effect in an insect model. Sci Rep. 2017; 7: 12429. [CrossRef]
  106. Yazaki K, Yoshikoshi C, Oshiro S, Yanase S. Supplemental cellular protection by a carotenoid extends lifespan via Ins/IGF-1 signaling in Caenorhabditis elegans. Oxid Med Cell Longev. 2011; 2011: 596240. [CrossRef]
  107. Lashmanova E, Proshkina E, Zhikrivetskaya S, Shevchenko O, Marusich E, Leonov S, et al. Fucoxanthin increases lifespan of Drosophila melanogaster and Caenorhabditis elegans. Pharmacol Res. 2015; 100: 228-241. [CrossRef]
  108. Weinrich T, Xu Y, Wosu C, Harvey PJ, Jeffery G. Mitochondrial function, mobility and lifespan are improved in Drosophila melanogaster by extracts of 9-cis-β-carotene from Dunaliella salina. Mar Drugs. 2019; 17: 279. [CrossRef]
  109. Wang X, Li X, Li L, Yang X, Wang J, Liu X, et al. Hawthorn fruit extract ameliorates H2O2-induced oxidative damage in neuronal PC12 cells and prolongs the lifespan of Caenorhabditis elegans via the IIS signaling pathway. Food Funct. 2022; 13: 10680-10694. [CrossRef]
  110. Urbizo-Reyes U, Kim KH, Reddivari L, Anderson JM, Liceaga AM. Oxidative stress protection by canary seed (Phalaris canariensis L.) peptides in Caco-2 Cells and Caenorhabditis elegans. Nutrients. 2022; 14: 2415. [CrossRef]
  111. Liu H, Wang Y, Zhang W, Sun W, Ji X, Zhang S, et al. Lentinan extends lifespan and increases oxidative stress resistance through DAF-16 and SKN-1 pathways in Caenorhabditis elegans. Int J Biol Macromol. 2022; 202: 286-295. [CrossRef]
  112. Bao K, Liu W, Song Z, Feng J, Mao Z, Bao L, et al. Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9. Elife. 2022; 11: e72410. [CrossRef]
  113. Tang R, Chen X, Dang T, Deng Y, Zou Z, Liu Q, et al. Lycium barbarum polysaccharides extend the mean lifespan of Drosophila melanogaster. Food Funct. 2019; 10: 4231-4241. [CrossRef]
  114. Cheng J, Wang H, Bartlett M, Stevenson D, Pan Y, Ho MS, et al. Antioxidant blend of curcumin and broccoli seed extract exhibits protective effect on neurodegeneration and promotes drosophila lifespan. ASN Neuro. 2021; 13: 17590914211015033. [CrossRef]
  115. Yue Y, Wang M, Feng Z, Zhu Y, Chen J. Antiaging effects of rice protein hydrolysates on Drosophila melanogaster. J Food Biochem. 2021; 45: e1360. [CrossRef]
  116. Tungmunnithum D, Abid M, Elamrani A, Drouet S, Addi M, Hano C. Almond skin extracts and chlorogenic acid delay chronological aging and enhanced oxidative stress response in yeast. Life. 2020; 10: 80. [CrossRef]
  117. Zahoor H, Watchaputi K, Hata J, Pabuprapap W, Suksamrarn A, Chua LS, et al. Model yeast as a versatile tool to examine the antioxidant and anti-ageing potential of flavonoids, extracted from medicinal plants. Front Pharmacol. 2022; 13: 980066. [CrossRef]
  118. Snell TW, Fields AM, Johnston RK. Antioxidants can extend lifespan of Brachionus manjavacas (Rotifera), but only in a few combinations. Biogerontology. 2012; 13: 261-275. [CrossRef]
  119. Harper JM, Holmes DJ. New perspectives on avian models for studies of basic aging processes. Biomedicines. 2021; 9: 649. [CrossRef]
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