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Cited by 145Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsAntioxidant Activity and Oxidative Stress

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

Open access
Varesi, Angelica, Chirumbolo, Salvatore, Campagnoli, Lucrezia Irene Maria, Pierella, Elisa, Piccini, Gaia Bavestrello, Carrara, Adelaide, Ricevuti, Giovanni, Scassellati, Catia +2 more·2022·Antioxidants
DOI 10.3390/antiox11071224PMC PMC9311946
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Abstract

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.

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Written from the paper’s full text.

TL;DR

This narrative review summarizes how oxidative stress drives cellular senescence and surveys antioxidant classes—enzymes, mitochondria-targeted compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, flavonoids, non-flavonoids, minerals, and melatonin—as potential anti-aging agents. It concludes that many show antioxidant, senolytic, or senomorphic promise, but evidence is mostly preclinical, dose- and context-dependent, and human validation remains limited.

Key findings

  • The review identifies multiple antioxidant categories with anti-senescence potential. Examples include CoQ10 supplementation (50 mg/kg/day) preventing osteoporosis in orchiectomized mice by limiting ROS and senescence; ubiquinol (250–300 mg/kg/day for at least 10 months) reducing senescence scores and ROS in SAMP1 mice but not improving lifespan; and SkQ1 (250 µmol/kg/day) preventing age-related immunological deterioration in senescence-prone rats.
  • Human evidence is sparse and sometimes inconclusive: lutein plus zeaxanthin (12 mg/day for one year) improved cognitive functions in elderly patients but not significantly versus placebo; plasma lycopene levels differed between young and old women in a study of 1973 participants; serum uric acid was 2-fold lower in 26 elderly participants versus 18 controls; and glycine plus N-acetylcysteine supplementation extended mouse lifespan by 24%.
  • Antioxidants can have dual pro-oxidant and antioxidant effects depending on dose, cell type, and exposure time; high doses may promote senescence. This is noted for compounds including β-carotene, resveratrol, uric acid, green tea, and fisetin, whose timing of administration may be crucial.
  • OS-induced senescence involves ROS/RNS imbalance, mitochondrial dysfunction, Nrf2/NF-κB, p53/p21, p16/Rb, and NAD+/sirtuin pathways. Antioxidants may act as senolytics or senomorphics, but optimal dosage, timing, and combinations remain unresolved.

Methods

  • Narrative review of published literature; no systematic search strategy, inclusion criteria, or meta-analysis is described.
  • Synthesizes in vitro, animal, and some human studies across antioxidant classes, citing references 1–479.
  • Main analysis is qualitative/narrative synthesis by antioxidant category; Tables 1–6 are cited in the text.

Limitations

  • Stated: most studies investigate a single compound in a particular cell line or animal model, which often prevents generalization and/or reproduction of results.
  • Stated: optimal dosage, administration window, treatment duration, and interactions among multiple antioxidants remain unclear; human studies are still lacking, and contradictory evidence exists for several compounds (e.g., GSH, resveratrol, p-coumaric acid, curcumin, melatonin).
  • Evident from the text: as a narrative review, it does not report a systematic search, risk-of-bias assessment, or quantitative synthesis; the cited tables are not included in the provided text.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/antiox11071224

Cites

477 of 477 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 385 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Increased oxidative stress is a major driver of senescence.

    “Increased oxidative stress (OS) is a further major driver of senescence [16,17,18,19,20,21].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [16] Gheitasi, 2020, Renoprotective Effects of Origanum Majorana Methanolic L and Carvacrol on Ischemia/Reperfusion-Induced Kidney Injury in Male Rats, Evid.-Based Complement. Altern. Med. source

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    • cites [17] Gholami, 2020, Functionalization of Graphene Oxide Nanosheets Can Reduce Their Cytotoxicity to Dental Pulp Stem Cells, J. Nanomater. source

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    • cites [18] Liguori, 2018, Oxidative Stress, Aging, and Diseases, Clin. Interv. Aging source

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    • cites [19] Omidifar, 2021, Trends in Natural Nutrients for Oxidative Stress and Cell Senescence, Oxidative Med. Cell. Longev. source

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    • cites [20] Corina, 2016, TNFA Gene Variants Related to the Inflammatory Status and Its Association with Cellular Aging: From the CORDIOPREV Study, Exp. Gerontol. source

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    • cites [21] Sriram, 2019, Oxidative Stress Mediates Depot-Specific Functional Differences of Human Adipose-Derived Stem Cells, Stem Cell Res. Ther. source

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  • Premisecitation

    Prolonged DNA damage response promotes senescence.

    “When the DNA damage response (DDR) is prolonged, it promotes senescence [4].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Krizhanovsky, 2021, Cellular Senescence in Ageing: From Mechanisms to Therapeutic Opportunities, Nat. Rev. Mol. Cell Biol. source

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  • Interpretationcitation

    Catalase is most probably a strong biomarker of senescence, due to the crucial role of H2O2 in modulating the OS response.

    “Catalase (CAT) is, most probably, a strong biomarker of senescence, due to the crucial role of H2O2 in modulating the OS response [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Cutler, 2005, Oxidative Stress and Aging: Catalase Is a Longevity Determinant Enzyme, Rejuvenation Res. source

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  • Premisecitation

    Oncogene activation partly via reactive oxygen species production determines hyperproliferation and altered DNA replication profiles.

    “oncogene activation partly via reactive oxygen species (ROS) production, determining hyperproliferation and altered DNA replication profiles [4,8]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Krizhanovsky, 2021, Cellular Senescence in Ageing: From Mechanisms to Therapeutic Opportunities, Nat. Rev. Mol. Cell Biol. source

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    • cites [8] Gao, X., Yu, X., Zhang, C., Wang, Y., Sun, Y., Sun, H., Zhang, H., Shi, Y., and He, X. (2022). Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-Related Diseases. Stem Cell Rev. Rep., 1–13. source

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  • Premisecitation

    A SASP profile can be promoted by failure of the antioxidant cascade due to defects in Nrf2.

    “a SASP profile can be promoted both by the failure of the antioxidant cascade due to defects in the well-known transcriptional factor Nrf2 (nuclear factor erythroid 2–related factor 2) [22]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Yu, 2021, The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging, Oxidative Med. Cell. Longev. source

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    Premisecitation

    When senescent cells persist, their SASP profile becomes damaging and can transform senescent fibroblasts into pro-inflammatory cells, thereby promoting tumour progression.

    “However, when senescent cells persist, their SASP profile becomes damaging, and this can transform senescent fibroblasts into pro-inflammatory cells, thereby promoting tumour progression [2,3].”
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    • cites [2] Calcinotto, 2019, Cellular Senescence: Aging, Cancer, and Injury, Physiol. Rev. source

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    • cites [3] Gorgoulis, 2019, Cellular Senescence: Defining a Path Forward, Cell source

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    Premisecitation

    SOD activity can change metal specificity to fit different requests from cells in different microenvironments and functional conditions.

    “Their activity has a dynamic nature, as they can change metal specificity to fit the different requests from cells in different microenvironments and functional conditions [32].”
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    • cites [32] Frye, 2022, Old Dogs, New Tricks: New Insights into the Iron/Manganese Superoxide Dismutase Family, J. Inorg. Biochem. source

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    Premisecitation

    Senescent fibroblasts rapidly develop growth arrest, changes in morphology and function, increased ROS production with marked up-regulation of SOD2 in transcripts and proteomics.

    “These senescent fibroblasts rapidly develop a growth arrest, changes in morphology and function, increased ROS production with a marked up-regulation of SOD2 in terms of both transcripts and proteomics [36,37,38].”
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    • cites [36] Allen, 1999, Differences in Electron Transport Potential, Antioxidant Defenses, and Oxidant Generation in Young and Senescent Fetal Lung Fibroblasts (WI-38), J. Cell Physiol source

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    • cites [37] Borlon, 2007, The Gene Expression Profile of Psoralen plus UVA-Induced Premature Senescence in Skin Fibroblasts Resembles a Combined DNA-Damage and Stress-Induced Cellular Senescence Response Phenotype, Exp. Gerontol. source

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    • cites [38] Lu, 1999, Oxidative Damage Elicited by Imbalance of Free Radical Scavenging Enzymes Is Associated with Large-Scale MtDNA Deletions in Aging Human Skin, Mutat. Res./Fundam. Mol. Mech. Mutagenesis source

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    Premisecitation

    When a switch from Mn2+ to Fe2+ in SOD2 occurs, the new FeSOD2 turns its function towards a pro-oxidant peroxidase and is a powerful causative factor of OS, mitochondria functional impairment and senescence.

    “When a switch from manganese (Mn2+) to iron (Fe2+) in SOD2 occurs, usually when due to a depletion Mn2+ is replaced by Fe2+, the new FeSOD2, which turns its function towards a pro-oxidant peroxidase, is a powerful causative factor of OS, mitochondria functional impairment and senescence [47].”
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    • cites [47] Ganini, 2018, Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice, Cell Chem. Biol. source

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    Premisecitation

    SODs represent a wide group of antioxidant enzymes with complex activities.

    “The superoxide dismutases (SODs) represent a wide group of antioxidant enzymes with complex activities [31,32].”
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    • cites [31] Miller, 2012, Superoxide Dismutases: Ancient Enzymes and New Insights, FEBS Lett. source

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    • cites [32] Frye, 2022, Old Dogs, New Tricks: New Insights into the Iron/Manganese Superoxide Dismutase Family, J. Inorg. Biochem. source

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    Premisecitation

    Persistent DDR activation at telomeres is sufficient to activate replicative cell senescence.

    “persistent DDR activation at telomeres, the ends of chromosomes, which is sufficient to activate replicative cell senescence [8]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Gao, X., Yu, X., Zhang, C., Wang, Y., Sun, Y., Sun, H., Zhang, H., Shi, Y., and He, X. (2022). Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-Related Diseases. Stem Cell Rev. Rep., 1–13. source

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    Premisecitation

    Skin aging is characterized by impaired wound healing, atrophy, reduced tensile strength and wrinkle formation, marked loss in skin structural integrity and in collagen and elastic fibres, with weakening in the fibre network, due to dysfunctional fibroblasts.

    “Particularly for skin aging, an event characterized by impaired wound healing, atrophy, reduced tensile strength and wrinkle formation, a marked loss in skin structural integrity and in collagen and elastic fibres, with weakening in the fibre network, has been reported, due to dysfunctional fibroblasts [34,35].”
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    • cites [34] Fisher, 2008, Looking Older, Arch. Dermatol. source

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    • cites [35] Quan, 2010, Reduced Expression of Connective Tissue Growth Factor (CTGF/CCN2) Mediates Collagen Loss in Chronologically Aged Human Skin, J. Investig. Dermatol. source

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    Premisecitation

    Senomorphics revert or slow down senescence by regulating the SASP.

    “senomorphics revert or slow down senescence by regulating the SASP [29]”
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    • cites [29] Elsallabi, O., Patruno, A., Pesce, M., Cataldi, A., Carradori, S., and Gallorini, M. (2022). Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection. Molecules, 27. source

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    Premisecitation

    The theory of mitochondrial free radicals in senescence proposes that progressive mitochondrial dysfunction, which occurs with aging, results in an increased production of ROS, which in turn causes further mitochondrial and global cellular damage.

    “The theory of mitochondrial free radicals in senescence proposes that progressive mitochondrial dysfunction, which occurs with aging, results in an increased production of ROS, which in turn causes further mitochondrial and global cellular damage.”
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    • cites [46] Hajam, Y.A., Rani, R., Ganie, S.Y., Sheikh, T.A., Javaid, D., Qadri, S.S., Pramodh, S., Alsulimani, A., Alkhanani, M.F., and Harakeh, S. (2022). Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells, 11. source

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    Premisecitation

    The T-allele of rs2284659 in the promoter region of SOD3 has been related to a safer plasma redox balance, leading to an improvement in cardiovascular outcome in patients with type 2 diabetes.

    “Interestingly, the T-allele of rs2284659 in the promoter region of SOD3 has been related to a safer plasma redox balance, leading to an improvement in the cardiovascular outcome in patients with type 2 diabetes [42].”
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    • cites [42] Mohammedi, 2015, Plasma Extracellular Superoxide Dismutase Concentration, Allelic Variations in the SOD3 Gene and Risk of Myocardial Infarction and All-Cause Mortality in People with Type 1 and Type 2 Diabetes, Cardiovasc. Diabetol. source

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    Interpretationcitation

    The Mn-Fe cross-talk may be impaired during aging, as when fibroblasts accumulate iron during development of a senescent phenotype, they may increase the Mn-Fe shift in SOD2.

    “This cross-talk may be impaired during aging, as, for instance, when fibroblasts accumulate iron during the development of a senescent phenotype [50], they may increase the Mn-Fe shift in SOD2, given that aging is also characterized by Mn and further micronutrients deficiency [51].”
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    • cites [50] Killilea, 2003, Iron Accumulation During Cellular Senescence in Human Fibroblasts In Vitro, Antioxid. Redox Signal. source

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    • cites [51] Killilea, 2008, A Connection between Magnesium Deficiency and Aging: New Insights from Cellular Studies, Magnes Res.

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    Premisecitation

    An increase in ROS/RNS levels can be determined by mitochondrial dysfunctions and can contribute to telomere damage and epigenetic modifications.

    “an increase in ROS/RNS levels can be determined by mitochondrial dysfunctions, and this can contribute to telomere damage and epigenetic modifications [27]”
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    • cites [27] Chapman, 2019, Mitochondrial Dysfunction and Cell Senescence: Deciphering a Complex Relationship, FEBS Lett. source

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    Premisecitation

    Senolytics mechanisms include inhibition of the BCL-2 antiapoptotic family, negative modulation of the PI3K/Akt pathway and FOXO regulation.

    “inhibition of the BCL-2 antiapoptotic family, negative modulation of the PI3K/Akt pathway and FOXO regulation [28]”
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    • cites [28] Zhu, 2020, Advancements in Therapeutic Drugs Targeting of Senescence, Ther. Adv. Chronic Dis. source

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    Premisecitation

    In vitro studies on human skin fibroblasts exposed to H2O2 have shown that cell treatment with CoQ10 significantly reduced OS, decreased SA-β gal positive cells and restored collagen type I protein and senescence-associated MMP production, therefore delaying skin aging.

    “In vitro studies conducted on human skin fibroblasts exposed to H2O2 have shown that cell treatment with CoQ10 significantly reduced OS, decreased the amount of SA-β gal positive cells and restored collagen type I protein and the senescence-associated matrix metalloproteinase (MMP) production, therefore delaying skin aging [63].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Mine, 2021, Protective Effects of Coenzyme Q10 on Cell Damage Induced by Hydrogen Peroxides in Cultured Skin Fibroblasts, J. Clin. Biochem. Nutr. source

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    Premisecitation

    Treatment with CoQ10H2 of H2O2-induced senescent HUVEC is effective in reducing SA-β gal, SASP release and ROS production, but enhanced NO and eNOS levels.

    “For example, a study conducted by Huo et al. has shown that treatment with CoQ10H2 of H2O2-induced senescent human umbilical vein endothelial cells (HUVEC) is effective in reducing SA-β gal, SASP release and ROS production, but enhanced nitric oxide (NO) and endothelial NO synthase (eNOS) levels [67].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Huo, 2018, Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in Vascular Endothelial Cells, Oxidative Med. Cell. Longev. source

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    Premisecitation

    Old mice subjected to a high CoQ10 diet displayed reduced OS in various tissues and were more efficient in performing the Morris water maze test compared to the untreated counterpart.

    “In this respect, results from a study designed to address CoQ10 administration only later in life showed that old mice subjected to a high CoQ10 diet displayed reduced OS in various tissues and were more efficient in performing the Morris water maze test compared to the untreated counterpart [95].”
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    • cites [95] Shetty, 2013, Coenzyme Q10 Supplementation Reverses Age-Related Impairments in Spatial Learning and Lowers Protein Oxidation, Age source

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    Premisecitation

    Coenzyme Q10, SkQ1, mitoquinone and methylene blue are among mitochondria targeted antioxidants exerting a role in counteracting OS-induced senescence, with CoQ10 being the most studied.

    “Coenzyme Q10 (CoQ10), SkQ1 (a.k.a. visomitin), mitoquinone (MitoQ) and methylene blue are among the mitochondria targeted antioxidants exerting a role in counteracting OS-induced senescence, with CoQ10 being the most studied (Table 1 and Table 2) [57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82].”
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    • cites [57] Ahmed, 2015, Mitochondrial Targeted Antioxidant in Cerebral Ischemia, J. Neurol. Neurosci. source

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    • cites [58] Blackmore, 2013, Coenzyme Q10 Prevents Accelerated Cardiac Aging in a Rat Model of Poor Maternal Nutrition and Accelerated Postnatal Growth, Mol. Metab. source

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    • cites [59] Chen, 2019, Coenzyme Q10 Alleviates Chronic Nucleoside Reverse Transcriptase Inhibitor-Induced Premature Endothelial Senescence, Cardiovasc. Toxicol. source

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    • cites [60] Ma, 2014, Inhibition of Stress Induced Premature Senescence in Presenilin-1 Mutated Cells with Water Soluble Coenzyme Q10, Mitochondrion source

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    • cites [61] Xue, 2017, Coenzyme Q10 Inhibits the Activation of Pancreatic Stellate Cells through PI3K/AKT/MTOR Signaling Pathway, Oncotarget source

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    • cites [62] Wu, 2020, CoQ10 Suppression of Oxidative Stress and Cell Senescence Increases Bone Mass in Orchiectomized Mice, Am. J. Transl. Res.

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    • cites [63] Mine, 2021, Protective Effects of Coenzyme Q10 on Cell Damage Induced by Hydrogen Peroxides in Cultured Skin Fibroblasts, J. Clin. Biochem. Nutr. source

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    • cites [64] Zhang, 2015, Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/MTOR Signaling, Oxidative Med. Cell. Longev. source

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    • cites [65] Velichkovska, 2019, Targeted Mitochondrial COQ10 Delivery Attenuates Antiretroviral-Drug-Induced Senescence of Neural Progenitor Cells, Mol. Pharm. source

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    • cites [66] Marcheggiani, 2021, Anti-Ageing Effects of Ubiquinone and Ubiquinol in a Senescence Model of Human Dermal Fibroblasts, Free Radic. Biol. Med. source

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    Premisecitation

    Although beneficial, lifelong supplementation with CoQ10 may also be deleterious.

    “Although beneficial, lifelong supplementation with CoQ10 may also be deleterious [92,93,94].”
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    • cites [92] Sohal, 2006, Effect of Coenzyme Q10 Intake on Endogenous Coenzyme Q Content, Mitochondrial Electron Transport Chain, Antioxidative Defenses, and Life Span of Mice, Free Radic. Biol. Med. source

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    • cites [93] Sumien, 2009, Prolonged Intake of Coenzyme Q10 Impairs Cognitive Functions in Mice, J. Nutr. source

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    • cites [94] Mcdonald, 2005, Concurrent Administration of Coenzyme Q10 and α-Tocopherol Improves Learning in Aged Mice, Free Radic. Biol. Med. source

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    Premisecitation

    CoQ10 deficiency has been linked to increased p21 expression, enhanced SASP production and downregulation of collagen type I and elastin.

    “Regarding senescence, CoQ10 deficiency has also been linked to increased p21 expression (a regulator of cell cycle progression), enhanced SASP production and downregulation of some extracellular matrix components (collagen type I and elastin) [66].”
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    • cites [66] Marcheggiani, 2021, Anti-Ageing Effects of Ubiquinone and Ubiquinol in a Senescence Model of Human Dermal Fibroblasts, Free Radic. Biol. Med. source

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    Premisecitation

    AD-related cognitive decline, behavioural test scores and senescence-associated myocardial disease may improve in murine models upon long-term or limited intake of SkQ1.

    “Finally, AD-related cognitive decline, behavioural test scores and senescence-associated myocardial disease may improve in murine models upon long-term (lifelong) or limited (between 12 and 18 months of age) intake of SkQ1 [77,78,99,100,101].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [77] Manskikh, 2015, Age-Associated Murine Cardiac Lesions Are Attenuated by the Mitochondria-Targeted Antioxidant SkQ1, Histol. Histopathol.

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    • cites [78] Stefanova, 2013, Alzheimer’s Disease-Like Pathology in Senescence-Accelerated OXYS Rats Can Be Partially Retarded with Mitochondria-Targeted Antioxidant SkQ1, J. Alzheimer’s Dis. source

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    • cites [99] Stefanova, 2019, Suppression of Alzheimer’s Disease-Like Pathology Progression by Mitochondria-Targeted Antioxidant SkQ1: A Transcriptome Profiling Study, Oxidative Med. Cell. Longev. source

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    • cites [100] Muraleva, N.A., Stefanova, N.A., and Kolosova, N.G. (2020). SkQ1 Suppresses the P38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats. Antioxidants, 9. source

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    • cites [101] Loshchenova, 2015, Influence of Antioxidant SkQ1 on Accumulation of Mitochondrial DNA Deletions in the Hippocampus of Senescence-Accelerated OXYS Rats, Biochemistry

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    Premisecitation

    Methylene blue is particularly effective in delaying skin cellular senescence and extending fibroblasts lifespan in vitro, as well as in improving mitochondrial functions.

    “Methylene blue is reported to be particularly effective in delaying skin cellular senescence and extending fibroblasts lifespan in vitro, as well as in improving mitochondrial functions [79,80].”
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    • cites [79] Atamna, 2008, Methylene Blue Delays Cellular Senescence and Enhances Key Mitochondrial Biochemical Pathways, FASEB J. source

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    • cites [80] Xiong, 2017, Anti-Aging Potentials of Methylene Blue for Human Skin Longevity, Sci. Rep. source

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    Premisecitation

    Ascorbic acid extends replicative lifespan of human embryonic fibroblasts by restoring age-related decline of mitochondrial function and lowering cellular ROS, therefore reducing mitochondrial and DNA damages with decelerated telomere shortening.

    “For example, AA has been reported to extend replicative lifespan of human embryonic fibroblasts by restoring age-related decline of mitochondrial function and lowering cellular ROS, therefore reducing mitochondrial and DNA damages with decelerated telomere shortening [123,124].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [123] Hwang, 2007, Ascorbic Acid Extends Replicative Life Span of Human Embryonic Fibroblast by Reducing DNA and Mitochondrial Damages, Nutr. Res. Pract. source

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    • cites [124] Furumoto, 1998, Age-Dependent Telomere Shortening Is Slowed down by Enrichment of Intracellular Vitamin C via Suppression of Oxidative Stress, Life Sci. source

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    Premisecitation

    Methylene blue may also prevent senescence and OS in primary retinal ganglion cells and mesenchymal stem cells, but its efficacy on stem cells remains limited to the cellular fraction characterized by a lower baseline level of OS.

    “Besides skin aging, MB may also prevent senescence and OS in other cell types, such as primary retinal ganglion cells and mesenchymal stem cells (MSCs), but its efficacy on stem cells remains limited to the cellular fraction characterized by a lower baseline level of OS [81,82].”
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    • cites [81] Bertolo, 2017, Oxidative Status Predicts Quality in Human Mesenchymal Stem Cells, Stem Cell Res. Ther. source

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    • cites [82] Daudt, 2012, Methylene Blue Protects Primary Rat Retinal Ganglion Cells from Cellular Senescence, Investig. Opthalmol. Vis. Sci. source

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    Premisecitation

    Supplementation of ascorbic acid appears to prevent OS, immunosenescence, telomere attrition, disorganization of chromatin, and excessive secretion of inflammatory factors, and to prolong life.

    “Supplementation of AA also appears to prevent OS, immunosenescence, telomere attrition, disorganization of chromatin, and excessive secretion of inflammatory factors, and to prolong life [122].”
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    • cites [122] Uchio, 2015, High Dietary Intake of Vitamin C Suppresses Age-Related Thymic Atrophy and Contributes to the Maintenance of Immune Cells in Vitamin C-Deficient Senescence Marker Protein-30 Knockout Mice, Br. J. Nutr. source

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    Premisecitation

    Multiple mechanisms are thought to underlie methylene blue antioxidant function, including Keap/Nrf2 pathway upregulation, MB to MBH2 cycling in mitochondria, complex IV induction and increased production of collagen 2A1 and elastin.

    “Although not yet fully understood, multiple mechanisms are thought to underlie its antioxidant function, including Keap/Nrf2 pathway upregulation, MB to MBH2 (the reduced form of MB) cycling in mitochondria, complex IV induction and increased production of collagen 2A1 and elastin, two components of the extracellular matrix fundamental for skin preservation [79,80,104].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [79] Atamna, 2008, Methylene Blue Delays Cellular Senescence and Enhances Key Mitochondrial Biochemical Pathways, FASEB J. source

      Not checked in the free run.

    • cites [80] Xiong, 2017, Anti-Aging Potentials of Methylene Blue for Human Skin Longevity, Sci. Rep. source

      Not checked in the free run.

    • cites [104] Atamna, 2015, Combined Activation of the Energy and Cellular-Defense Pathways May Explain the Potent Anti-Senescence Activity of Methylene Blue, Redox Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vitamin A and retinoic acid administration improve Alzheimer's disease and age-related attenuation of memory/learning in mouse models, probably due to immunomodulatory effect and reduction of pro-inflammatory cytokines and chemokines production by astrocytes and microglia, as well as promotion of differentiation of neural stem cells and regeneration of neural cells.

    “Vitamin A and retinoic acid (a metabolite of all-trans-retinol) administration have been demonstrated to improve AD and age-related attenuation of memory/learning in mouse models, and this is probably due to their immunomodulatory effect and the reduction of pro-inflammatory cytokines and chemokines production by astrocytes and microglia, as well as to the promotion of differentiation of neural st”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [108] Shudo, 2009, Towards Retinoid Therapy for Alzheimers Disease, Curr. Alzheimer Res. source

      Not checked in the free run.

    • cites [109] Kitaoka, 2013, The Retinoic Acid Receptor Agonist Am80 Increases Hippocampal ADAM10 in Aged SAMP8 Mice, Neuropharmacology source

      Not checked in the free run.

    • cites [110] Fukasawa, 2012, Tamibarotene: A Candidate Retinoid Drug for Alzheimer’s Disease, Biol. Pharm. Bull. source

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  • May combine two claims.

    Premisecitation

    SkQ1 and SkQR1 reduce H2O2-induced senescence and apoptosis in vitro and prevent senescence and tissue damage during aging.

    “In particular, SkQ1 and SkQR1 have been reported to reduce H2O2-induced senescence and apoptosis in vitro and to prevent senescence and tissue damage during aging [75].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] Skulachev, 2011, Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies, Curr. Drug Targets source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In SAMP1 mice, ubiquinol administration at 250-300 mg/kg/day for at least 10 months can reduce senescence grading scores and ROS production, while enhancing antioxidant defences.

    “In vivo, experiments conducted on SAMP1 mice reported that ubiquinol administration at relatively high doses (250–300 mg/kg/day) for at least 10 months can reduce senescence grading scores and ROS production, while enhancing antioxidant defences [68,70].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [68] Yan, 2006, Reduced Coenzyme Q10 Supplementation Decelerates Senescence in SAMP1 Mice, Exp. Gerontol. source

      Not checked in the free run.

    • cites [70] Maruoka, 2014, Long-Term Effect of Ubiquinol on Exercise Capacity and the Oxidative Stress Regulation System in SAMP1 Mice, J. Phys. Ther. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Data on extended fibroblast lifespan are debated, with some evidence showing that they can successfully decelerate aging and prevent senescence while other studies are inconclusive.

    “In this respect, for example, data on extended fibroblast lifespan are debated, with some evidence showing that they can successfully decelerate aging and prevent senescence while other studies are inconclusive [105].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [105] Bartosz, 2020, Effect of Antioxidants on the Fibroblast Replicative Lifespan In Vitro, Oxidative Med. Cell. Longev.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SkQ1 exerts its antioxidant properties by fatty acid co-mediated uncoupling, through interference with lipoperoxyl radicals and via regulating electron flow at the level of mitochondria.

    “Mechanistically, SkQ1 exerts its antioxidant properties by fatty acid co-mediated uncoupling, through interference with lipoperoxyl radicals and via regulating the electron flow at the level of mitochondria [102].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] 2017, Antioxidant Mechanism of Mitochondria-Targeted Plastoquinone SkQ1 Is Suppressed in Aglycemic HepG2 Cells Dependent on Oxidative Phosphorylation, Biochim. Biophys. Acta (BBA)-Bioenerg. source

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  • May combine two claims.

    Premisecitation

    Ascorbic acid has a protective effect on human chondrocytes against OS by attenuating the increase of apoptosis, the loss of viability and the increase of senescence, and therefore hindering the development of osteoarthritis and aging of cartilage.

    “Moreover, AA was found to have a protective effect also on human chondrocytes against OS by attenuating the increase of apoptosis, the loss of viability and the increase of senescence, and therefore hindering the development of osteoarthritis and aging of cartilage [125,126].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [125] Chang, 2015, Ascorbic Acid Provides Protection for Human Chondrocytes against Oxidative Stress, Mol. Med. Rep. source

      Not checked in the free run.

    • cites [126] Burger, M., Steinitz, A., Geurts, J., Pippenger, B., Schaefer, D., Martin, I., Barbero, A., and Pelttari, K. (2017). Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cellular pretreatment with lycopene protects MSCs against H2O2-induced senescence, enhances antioxidant defences (improved MnSOD activity and reduced ROS production) and prevents apoptosis through the modulation of Bax and Bak proteins.

    “Similarly, studies conducted on MSCs demonstrated that cellular pretreatment with lycopene protects against H2O2-induced senescence, enhances antioxidant defences (i.e., improved MnSOD activity and reduced ROS production) and prevents apoptosis through the modulation of Bax and Bak proteins [172].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [172] Kim, 2015, Pretreatment with Lycopene Attenuates Oxidative Stress-Induced Apoptosis in Human Mesenchymal Stem Cells, Biomol. Ther. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Warfarin, a vitamin K antagonist, induces chronic low-grade inflammation in non-senescent vascular smooth muscle cells and enhances vascular aging and calcification, especially in young patients (<65 years old).

    “Accordingly, warfarin, a vitamin K antagonist, has been found to induce chronic low-grade inflammation in non-senescent vascular smooth muscle cells and enhance vascular aging and calcification, especially in young patients (<65 years old) [139,140].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [139] Wei, 2020, Warfarin Accelerates Aortic Calcification by Upregulating Senescence-Associated Secretory Phenotype Maker Expression, Oxidative Med. Cell. Longev. source

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    • cites [140] Ikeda, 2009, Replicative Senescence of Vascular Smooth Muscle Cells Enhances the Calcification through Initiating the Osteoblastic Transition, Am. J. Physiol. Heart Circ. Physiol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Higher consumption of antioxidants such as vitamin E is able to reduce ROS levels, leading to decreased telomere shortening, decelerating cellular senescence, and potentially decreasing the risk of disease development.

    “It has been recently observed that a higher consumption of antioxidants such as vitamin E is able to reduce ROS levels, leading to decreased telomere shortening, decelerating the cellular senescence, and potentially decreasing the risk of disease development [132,133].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [132] Shen, 2009, Telomere Length, Oxidative Damage, Antioxidants and Breast Cancer Risk, Int. J. Cancer source

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    • cites [133] Corina, 2019, Low Intake of Vitamin E Accelerates Cellular Aging in Patients With Established Cardiovascular Disease: The CORDIOPREV Study, J. Gerontol. Ser. A source

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  • May combine two claims.

    Premisecitation

    During aging, lycopene protects from cognitive impairment, insulin resistance and cancer, among the others.

    “During aging, lycopene protects from cognitive impairment, insulin resistance and cancer, among the others [169,170,171].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [169] Chen, 2015, Lycopene and Risk of Prostate Cancer, Medicine source

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    • cites [170] Li, 2022, Lycopene Ameliorates Insulin Resistance and Increases Muscle Capillary Density in Aging via Activation of SIRT1, J. Nutr. Biochem. source

      Not checked in the free run.

    • cites [171] Chen, 2019, A Review for the Pharmacological Effect of Lycopene in Central Nervous System Disorders, Biomed. Pharmacother. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Improved cognitive functions were observed in elderly patients supplemented for one year with a mixture of lutein and zeaxanthin (12 mg/day), albeit not significant compared to the placebo group.

    “Accordingly, improved cognitive functions were observed in elderly patients supplemented for one year with a mixture of lutein and zeaxanthin (12 mg/day), albeit not significant compared to the placebo group [162,163].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [162] Lindbergh, 2018, Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial, J. Int. Neuropsychol. Soc. source

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    • cites [163] Mewborn, 2019, The Effects of Lutein and Zeaxanthin Supplementation on Brain Morphology in Older Adults: A Randomized, Controlled Trial, J. Aging Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OS-induced senescence is involved in the pathogenesis of age-related macular degeneration (AMD), which represents the leading cause of blindness in aged individuals.

    “There is evidence that OS-induced senescence is involved in the pathogenesis of age-related macular degeneration (AMD), which represents the leading cause of blindness in aged individuals [158,164,165].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [158] Li, L.H., Lee, J.C.-Y., Leung, H.H., Lam, W.C., Fu, Z., and Lo, A.C.Y. (2020). Lutein Supplementation for Eye Diseases. Nutrients, 12. source

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    • cites [164] Chae, 2018, Lutein Protects Human Retinal Pigment Epithelial Cells from Oxidative Stress-induced Cellular Senescence, Mol. Med. Rep.

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    • cites [165] Sommerburg, 1998, Fruits and Vegetables That Are Sources for Lutein and Zeaxanthin: The Macular Pigment in Human Eyes, Br. J. Ophthalmol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In vitro, keratinocytes treatment with β-carotene, prior to UVA exposure, prevents the upregulation of MMP-1, MMP-3 and MMP-10, suggesting a protective role of β-carotene against OS-induced senescence.

    “In vitro, keratinocytes treatment with β-carotene, prior to UVA exposure, prevents the upregulation of MMP-1, MMP-3 and MMP-10, therefore suggesting a protective role of β-carotene against OS-induced senescence [154].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [154] Wertz, 2004, β-Carotene Inhibits UVA-Induced Matrix Metalloprotease 1 and 10 Expression in Keratinocytes by a Singlet Oxygen-Dependent Mechanism, Free Radic. Biol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Multiple carotenoids might be responsible for the antioxidant effects reported in the literature, but more research is needed to clarify the optimal combination of these supplements.

    “These results indicate that multiple carotenoids might be responsible for the antioxidant effects reported in the literature, but more research is needed to clarify the optimal combination of these supplements.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Glutathione exists in two forms, reduced glutathione (GSH) and oxidized glutathione (GSSG), which are interconverted by GPx and glutathione reductase.

    “Glutathione can exist in two forms: reduced glutathione (GSH) and oxidized glutathione (GSSG), which are converted into each other by the enzymatic activity of GPx (that links two GSH in one GSSG through the formation of a disulphide bond) and glutathione reductase (that catalyses the reduction of one GSSG into two GSH to the expenses of NADPH) [177].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [177] Lv, 2019, Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy, Oxidative Med. Cell. Longev. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    β-carotene is the precursor of retinoic acid.

    “β-carotene is the precursor of retinoic acid [154,155].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [154] Wertz, 2004, β-Carotene Inhibits UVA-Induced Matrix Metalloprotease 1 and 10 Expression in Keratinocytes by a Singlet Oxygen-Dependent Mechanism, Free Radic. Biol. Med. source

      Not checked in the free run.

    • cites [155] Fiedor, 2014, Potential Role of Carotenoids as Antioxidants in Human Health and Disease, Nutrients source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Glutathione is a natural tripeptide (γ-l-glutamyl-l-cysteinylglycine) with a fundamental role in the regulation of redox homeostasis.

    “Glutathione is a natural tripeptide, that is γ-l-glutamyl-l-cysteinylglycine, harbouring a fundamental role in the regulation of redox homeostasis [176].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [176] Gaucher, C., Boudier, A., Bonetti, J., Clarot, I., Leroy, P., and Parent, M. (2018). Glutathione: Antioxidant Properties Dedicated to Nanotechnologies. Antioxidants, 7. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inhibiting or reducing GSH synthesis is sufficient to induce premature senescence and OS-mediated telomere shortening in HUVEC, and this condition is not restored by telomerase activity.

    “For example, inhibiting or reducing GSH synthesis is sufficient to induce premature senescence and OS-mediated telomere shortening in HUVEC, and this condition is not restored by telomerase activity [187].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [187] Kurz, 2004, Chronic Oxidative Stress Compromises Telomere Integrity and Accelerates the Onset of Senescence in Human Endothelial Cells, J. Cell Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Normal aging and cellular senescence are conditions influenced by oxidative stress.

    “both conditions influenced by OS [183,184,185,186].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [183] Morin, 2019, Hsp22 Overexpression Induces Myocardial Hypertrophy, Senescence and Reduced Life Span through Enhanced Oxidative Stress, Free Radic. Biol. Med. source

      Not checked in the free run.

    • cites [184] Armeni, T., Ercolani, L., Urbanelli, L., Magini, A., Magherini, F., Pugnaloni, A., Piva, F., Modesti, A., Emiliani, C., and Principato, G. (2012). Cellular Redox Imbalance and Changes of Protein S-Glutathionylation Patterns Are Associated with Senescence Induced by Oncogenic H-Ras. PLoS ONE, 7. source

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    • cites [185] Redondo, 2018, Dysregulation of Mesenchymal Stromal Cell Antioxidant Responses in Progressive Multiple Sclerosis, Stem Cells Transl. Med. source

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    • cites [186] Huang, 2022, Angiotensin II-Induced Erythrocyte Senescence Contributes to Oxidative Stress, Rejuvenation Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Elderly people (>74 years old) are generally characterized by reduced glutathione-S-transferase activity and slightly lower cerebrospinal fluid antioxidant defences compared to younger individuals.

    “At brain level, elderly people (>74 years old) are generally characterized by reduced glutathione-S-transferase activity accompanied by slightly lower cerebrospinal fluid (CSF) antioxidant defences compared to younger individuals [193].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [193] 2018, Analysis of Neurotrophic and Antioxidant Factors Related to Midbrain Dopamine Neuronal Loss and Brain Inflammation in the Cerebrospinal Fluid of the Elderly, Exp. Gerontol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Administration of glutathione precursors (glycine and cysteine) is sufficient to significantly increase GSH levels and reduce OS in aged individuals.

    “Similarly, the administration of glutathione precursors (i.e., glycine and cysteine) is sufficient to significantly increase GSH levels and reduce OS in aged individuals [200,201].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [200] Sekhar, 2011, Deficient Synthesis of Glutathione Underlies Oxidative Stress in Aging and Can Be Corrected by Dietary Cysteine and Glycine Supplementation, Am. J. Clin. Nutr. source

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    • cites [201] Sekhar, 2021, GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging, J. Nutr. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chronic serum hyperuricemia positively correlates with inflammation, DNA damage and OS, and has been implicated in pathogenesis of several disorders, including renal, metabolic, and cardiovascular diseases.

    “Accordingly, chronic serum hyperuricemia positively correlates with inflammation, DNA damage and OS, and has been implicated in the pathogenesis of several disorders, including renal, metabolic, and cardiovascular diseases [214,217,218].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [214] Roumeliotis, S., Roumeliotis, A., Dounousi, E., Eleftheriadis, T., and Liakopoulos, V. (2019). Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review. Nutrients, 11. source

      Not checked in the free run.

    • cites [217] Vazirpanah, 2015, Inflamm-Ageing and Senescence in Gout: The Tale of an Old King’s Disease, Curr. Aging Sci. source

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    • cites [218] Goldberg, 2015, Drivers of Age-Related Inflammation and Strategies for Healthspan Extension, Immunol. Rev. source

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  • May combine two claims.

    Premisecitation

    In vivo, 12-week dietary supplementation with S-allylcysteine (0.05% or 0.2%) to 60-week-old wild type mice reduces senescence, improves mitochondrial functions, and ameliorates both aging and OS biomarkers.

    “In vivo, 12-week dietary supplementation with S-allylcysteine (0.05% or 0.2%) to 60-week-old wild type mice reduces senescence, improves mitochondrial functions, and ameliorates both aging and OS biomarkers [209].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] Chen, 2022, S-Allylcysteine Ameliorates Aging Features via Regulating Mitochondrial Dynamics in Naturally Aged C57BL/6J Mice, Mol. Nutr. Food Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several studies have demonstrated a link between UA levels, OS, and cell cycle arrest, both in vitro and in vivo, and improved aging-related functions have been observed following administration of UA-lowering agents.

    “Concerning senescence, several studies have demonstrated a link between UA levels, OS, and cell cycle arrest, both in vitro and in vivo, and improved aging-related functions have been observed following the administration of UA lowering agents [219].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [219] Fan, 2016, Mechanism of Ginsenoside Rg1 Renal Protection in a Mouse Model of D-Galactose-Induced Subacute Damage, Pharm. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Insufficient bioavailability of GSH remains a limit for direct GSH delivery, and prodrugs and precursors of GSH have been proposed as an alternative route.

    “However, the insufficient bioavailability of GSH remains a limit, and the use of prodrugs and precursors of GSH have been proposed as an alternative route [198].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [198] Homma, 2015, Application of Glutathione as Anti-Oxidative and Anti-Aging Drugs, Curr. Drug Metab. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although UA is classified as an important antioxidant molecule when circulating in plasma, it exerts potent pro-oxidant activity once inside the cell or in the form of extracellular crystals.

    “In the context of OS, although UA is classified as an important antioxidant molecule when circulating in the plasma, it exerts a potent pro-oxidant activity once inside the cell or in the form of extracellular crystals, probably due to different environmental interactions [214,215].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [214] Roumeliotis, S., Roumeliotis, A., Dounousi, E., Eleftheriadis, T., and Liakopoulos, V. (2019). Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review. Nutrients, 11. source

      Not checked in the free run.

    • cites [215] 2018, The Pathophysiology of Uric Acid on Renal Diseases, Contrib. Neprhol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Supplementation with glycine and N-acetylcysteine ensures correct GSH balance and extends mice lifespan by 24%.

    “Recent data from Kumar et al. showed that supplementation with glycine and N-acetylcysteine ensures the correct GSH balance and extends mice lifespan by 24% [199].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [199] Kumar, P., Osahon, O.W., and Sekhar, R.V. (2022). GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Mice Increases Length of Life by Correcting Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Abnormalities in Mitophagy and Nutrient Sensing, and Genomic Damage. Nutrients, 14. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    S-1-propenylcysteine acts as an anti-inflammatory via stimulation of IL-10 expression and promotion of macrophage polarization towards an M2c status, which regulates phagocytosis of apoptotic cells.

    “For instance, recent evidence has shown that S-1-propenylcysteine, one of the AGE components, acts as an anti-inflammatory via stimulation of IL-10 expression and promotion of macrophage polarization towards an M2c status, which regulates the phagocytosis process of apoptotic cells [213].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [213] Miki, 2021, S-1-Propenylcysteine Promotes IL-10-Induced M2c Macrophage Polarization through Prolonged Activation of IL-10R/STAT3 Signaling, Sci. Rep. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Overall, various organosulfur compounds commonly found in onion and garlic extracts can prevent OS, supporting their usefulness in counteracting the aging process.

    “Overall, in line with the well-known beneficial effects of onion and garlic consumption, it is emerging that various organosulfur compounds commonly found in their extracts can prevent OS, thus supporting their usefulness in counteracting the aging process.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    SAMP8 mice fed for 2 months with a diet containing 2% aged garlic extract (AGE) show improved lifespan and learning scores compared to untreated counterparts.

    “Concerning aging, SAMP8 mice fed for 2 months with a diet containing 2% of aged garlic extract (AGE), which has been reported to have a higher antioxidant activity compared to fresh garlic extract [204], show improved lifespan and learning scores compared to the untreated counterpart [205,206,207].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [205] Moriguchi, 1996, Aged Garlic Extract Prolongs Longevity and Improves Spatial Memory Deficit in Senescence-Accelerated Mouse, Biol. Pharm. Bull. source

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    • cites [206] Moriguchi, 1994, Prolongation of Life Span and Improved Learning in the Senescence Accelerated Mouse Produced by Aged Garlic Extract, Biol. Pharm. Bull. source

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    • cites [207] Nishimura, 2006, Antioxidative Activity and Ameliorative Effects of Memory Impairment of Sulfur-Containing Compounds in Allium Species, BioFactors source

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  • May combine two claims.

    Premisecitation

    When used as a whole, garlic extract exerts strong NO scavenging function, reduces MMP-1 expression and ROS levels, inhibits SASP and improves SIRT1 activity, thus alleviating UVB-induced senescence in keratinocytes.

    “Still, when used as a whole, garlic extract exerts a strong NO scavenging function, reduces MMP-1 expression and ROS levels, inhibits SASP and improves SIRT1 activity, thus alleviating UVB-induced senescence in keratinocytes [212].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [212] Kim, H. (2016). Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human Keratinocytes. Nutrients, 8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    At the molecular level, AGE reduces ROS production, increases glutathione levels, enhances activity of SOD, CAT and GPx, prevents lipid peroxidation and inhibits NF-kB activity.

    “At the molecular level, AGE reduces the production of ROS, increases glutathione levels, enhances the activity of the main antioxidant enzymes SOD, CAT and GPx, prevents lipid peroxidation and inhibits NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity [203,210].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [203] El-Saber Batiha, G., Magdy Beshbishy, A., G. Wasef, L., Elewa, Y.H.A., A. Al-Sagan, A., Abd El-Hack, M.E., Taha, A.E., M. Abd-Elhakim, Y., and Prasad Devkota, H. (2020). Chemical Constituents and Pharmacological Activities of Garlic (Allium Sativum L.): A Review. Nutrients, 12. source

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    • cites [210] Borek, 2001, Antioxidant Health Effects of Aged Garlic Extract, J. Nutr. source

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  • May combine two claims.

    Premisecitation

    Quercetin is a flavonol known for its antioxidant, anti-inflammatory, antitumor, and senolytic properties.

    “Quercetin is a flavonol known for its antioxidant, anti-inflammatory, antitumor, and senolytic properties [258].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [258] Zhang, 2021, Quercetin Prevents Radiation-Induced Oral Mucositis by Upregulating BMI-1, Oxidative Med. Cell. Longev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In humans, a comparative study on 26 elderly participants and 18 controls reported a 2-fold reduction in serum UA levels in aged individuals compared to controls, in line with diminished antioxidant defences.

    “In humans, results from a comparative study conducted on 26 elderly participants and 18 controls reported a 2-fold reduction in serum UA levels in aged individuals compared to controls, and this pattern was in line with diminished antioxidant defences [225].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [225] Park, 2010, Senescence-Related Truncation and Multimerization of Apolipoprotein A-I in High-Density Lipoprotein With an Elevated Level of Advanced Glycated End Products and Cholesteryl Ester Transfer Activity, J. Gerontol. Ser. A: Biomed. Sci. Med. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment with quercetin significantly lowers levels of ROS and inflammatory cytokines, reduces expression of SA-β gal, p16 and p53, and markedly increases that of antioxidant enzymes SOD and CAT, regardless of the type of oxidative trigger used to induce senescence.

    “Results obtained on different cell lines show that treatment with quercetin significantly lowers the levels of ROS and inflammatory cytokines, reduces the expression of SA-β gal, p16 and p53 and markedly increases that of the antioxidant enzymes SOD and CAT, regardless of the type of oxidative trigger used to induce senescence [258,259,260,261,262].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [258] Zhang, 2021, Quercetin Prevents Radiation-Induced Oral Mucositis by Upregulating BMI-1, Oxidative Med. Cell. Longev. source

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    • cites [259] Smith, 2020, UVA Irradiation Increases Ferrous Iron Release from Human Skin Fibroblast and Endothelial Cell Ferritin: Consequences for Cell Senescence and Aging, Free Radic. Biol. Med. source

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    • cites [260] Li, 2018, Quercetin Protects against Ox-LDL-induced Injury via Regulation of ABCAl, LXR-α and PCSK9 in RAW264.7 Macrophages, Mol. Med. Rep.

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    • cites [261] Sohn, 2018, Restoring Effects of Natural Anti-Oxidant Quercetin on Cellular Senescent Human Dermal Fibroblasts, Am. J. Chin. Med. source

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    • cites [262] Zoico, 2021, Senolytic Effects of Quercetin in an in Vitro Model of Pre-Adipocytes and Adipocytes Induced Senescence, Sci. Rep. source

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  • May combine two claims.

    Premisecitation

    In vivo, 6-week oral administration of fisetin drastically reduced senescence, ROS, lipid peroxidation and protein oxidation in a rat model of induced aging, and lifespan extension has been reported in mice.

    “In vivo, 6-week oral administration of fisetin drastically reduced senescence, ROS, lipid peroxidation and protein oxidation in a rat model of induced aging, and lifespan extension has been reported in mice [235,272].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [235] Yousefzadeh, 2018, Fisetin Is a Senotherapeutic That Extends Health and Lifespan, EBioMedicine source

      Not checked in the free run.

    • cites [272] Singh, 2019, Fisetin, a Potential Caloric Restriction Mimetic, Attenuates Senescence Biomarkers in Rat Erythrocytes, Biochem. Cell Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fisetin is protective when administered in the presence of OS, but if given chronically in physiological conditions, it may cause telomere shortening and promote senescence.

    “If on the one hand fisetin is protective when administered in the presence of OS, if it is given chronically in physiological conditions, it may even cause telomere shortening, therefore promoting senescence [275].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [275] Boesten, 2013, Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1, Oxidative Med. Cell. Longev. source

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  • May combine two claims.

    Premisecitation

    Genistein reduces OS-induced senescence by mitigating levels of mitochondrial ROS and DNA oxidation marker 8-OHdG, and by upregulating the SIRT1-FOXO3 axis.

    “Mechanistically, genistein reduces OS-induced senescence by mitigating the levels of mitochondrial ROS and of the DNA oxidation marker 8-OHdG, as well as by upregulating the SIRT1-FOXO3 axis, which is known to prevent aging [278].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [278] Zhang, 2022, Genistein Suppresses Ox-LDL-elicited Oxidative Stress and Senescence in HUVECs through the SIRT1-p66shc-Foxo3a Pathways, J. Biochem. Mol. Toxicol. source

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  • May combine two claims.

    Premisecitation

    Beside antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, making them of interest as anti-aging compounds.

    “Beside the antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, which make them of great interest as anti-aging compounds (Table 3) [228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257].”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [228] Rufino, 2021, Flavonoids as Antiobesity Agents: A Review, Med. Res. Rev. source

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    • cites [229] Kim, 2010, Kaempferol Modulates Pro-Inflammatory NF-ΚB Activation by Suppressing Advanced Glycation Endproducts-Induced NADPH Oxidase, Age source

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    • cites [230] Hua, 2021, le Naringenin Alleviates Nonalcoholic Steatohepatitis in Middle-Aged Apoe−/−mice: Role of SIRT1, Phytomedicine source

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    • cites [231] Chattopadhyay, 2016, Context- and Dose-Dependent Modulatory Effects of Naringenin on Survival and Development of Drosophila Melanogaster, Biogerontology source

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    • cites [232] Zhu, 2015, The Achilles’ Heel of Senescent Cells: From Transcriptome to Senolytic Drugs, Aging Cell source

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    • cites [233] Ogrodnik, 2021, Whole-body Senescent Cell Clearance Alleviates Age-related Brain Inflammation and Cognitive Impairment in Mice, Aging Cell source

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    • cites [234] Dookun, 2022, Therapeutic Potential of Senolytics in Cardiovascular Disease, Cardiovasc. Drugs Ther. source

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    • cites [235] Yousefzadeh, 2018, Fisetin Is a Senotherapeutic That Extends Health and Lifespan, EBioMedicine source

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    • cites [236] Chen, 2011, Rapamycin and Other Longevity-Promoting Compounds Enhance the Generation of Mouse Induced Pluripotent Stem Cells, Aging Cell source

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    • cites [237] Perrott, 2017, Apigenin Suppresses the Senescence-Associated Secretory Phenotype and Paracrine Effects on Breast Cancer Cells, Geroscience source

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  • May combine two claims.

    Premisecitation

    Hesperidin attenuates senescence-related oxidative damage in cardiomyocytes, both independently and in combination with other molecules, through induction of Nrf2 and GST expression.

    “Its properties impact positively on cardiomyocytes as it attenuates senescence-related oxidative damage, both independently and in combination with other molecules, through the induction of Nrf2 and of GST expression [247,296,297].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [247] Elavarasan, 2012, Hesperidin-Mediated Expression of Nrf2 and Upregulation of Antioxidant Status in Senescent Rat Heart, J. Pharm. Pharmacol. source

      Not checked in the free run.

    • cites [296] Chularojmontri, 2013, Pummelo Protects Doxorubicin-Induced Cardiac Cell Death by Reducing Oxidative Stress, Modifying Glutathione Transferase Expression, and Preventing Cellular Senescence, Evid.-Based Complement. Altern. Med. source

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    • cites [297] Mulero, 2012, Variations on Cardiovascular Risk Factors in Metabolic Syndrome after Consume of a Citrus-Based Juice, Clin. Nutr. source

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  • May combine two claims.

    Premisecitation

    In vitro, human embryonic lung fibroblasts exposed to H2O2 or doxorubicin and subsequently treated with apigenin show reduced SA-β gal activity, cell cycle promotion, increased levels of SIRT1, CAT and SOD, and reduced expression of p21, p53 and p16 compared to untreated counterpart.

    “In vitro, human embryonic lung fibroblasts exposed to the pro-senescence stimuli H2O2 or doxorubicin, and subsequently treated with apigenin, show reduced SA-β gal activity, cell cycle promotion, increased levels of SIRT1, CAT and SOD and reduced expression of the senescence associated p21, p53 and p16 proteins compared to the untreated counterpart [308].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [308] Li, 2021, Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis, Am. J. Chin. Med. source

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  • May combine two claims.

    Premisecitation

    When combined with dasatinib, quercetin showed senolytic activity, improvement of physical function and increased lifespan in mice.

    “When combined with dasatinib (a tyrosine kinase inhibitor used as an antitumoral drug), quercetin showed senolytic activity, improvement of physical function and increased lifespan in mice [268].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [268] Xu, 2018, Senolytics Improve Physical Function and Increase Lifespan in Old Age, Nat. Med. source

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  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    In aging murine models, naringenin administration markedly stimulated Nrf2 activity and improved expression of antioxidant enzymes HO-1 and NADPH-quinone oxidoreductase 1, suggesting amelioration of behavioural and neurological dysfunctions.

    “The authors reported that naringenin administration markedly stimulated the activity of Nrf2 and improved the expression of the antioxidant enzymes HO-1 and NADPH-quinone oxidoreductase 1 [301].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [301] Zhang, 2017, Naringenin Ameliorates Behavioral Dysfunction and Neurological Deficits in a D-Galactose-Induced Aging Mouse Model Through Activation of PI3K/Akt/Nrf2 Pathway, Rejuvenation Res. source

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  • May combine two claims.

    Premisecitation

    Higher plasma UA levels in d-galactose rat models of accelerated aging were linked to decreased senescence and an increased SOD/(GPx + CAT) enzymatic ratio, indicative of antioxidant activity.

    “However, higher plasma UA levels in d-galactose rat models of accelerated aging were linked to decreased senescence and an increased SOD/(GPx + CAT) enzymatic ratio, which is indicative of antioxidant activity, thus confirming the beneficial role of UA when considered in the plasma [224].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [224] Mladenov, 2015, The Relationship Between Antioxidant Enzymes and Lipid Peroxidation in Senescent Rat Erythrocytes, Physiol. Res. source

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  • May combine two claims.

    Premisecitation

    CUR has been shown to improve cognitive deficits, suppress vascular aging and inflammation in elderly mice, and attenuate neuronal aging both in vitro and in vivo by downregulating p16 and p21 and upregulating antioxidant enzymes including SOD1, CAT and GPx.

    “Indeed, it has been shown to improve cognitive deficits, suppress vascular aging and inflammation in elderly mice, and attenuate neuronal aging both in vitro and in vivo by downregulating the expression of p16 and p21 and upregulating antioxidant enzymes, including SOD1, CAT and GPx [329,330,397].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [329] Sun, 2013, Neurobiological and Pharmacological Validity of Curcumin in Ameliorating Memory Performance of Senescence-Accelerated Mice, Pharmacol. Biochem. Behav. source

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    • cites [330] Takano, K., Tatebe, J., Washizawa, N., and Morita, T. (2018). Curcumin Inhibits Age-Related Vascular Changes in Aged Mice Fed a High-Fat Diet. Nutrients, 10. source

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    • cites [397] Lee, 2020, Curcumin and Hesperetin Attenuate D-Galactose-Induced Brain Senescence In Vitro and In Vivo, Nutr. Res. Pract. source

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  • May combine two claims.

    Premisecitation

    GA can reduce senescence markers in rat embryonic fibroblast cells, delay thymus involution in old mice, and protect cardiac cells from oxidative damage and senescence, enhancing GST expression.

    “Indeed, it has been shown that GA can reduce senescence markers in rat embryonic fibroblast cells, delay thymus involution in old mice, and protect cardiac cells from oxidative damage and senescence, enhancing GST expression [296,323,353].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [296] Chularojmontri, 2013, Pummelo Protects Doxorubicin-Induced Cardiac Cell Death by Reducing Oxidative Stress, Modifying Glutathione Transferase Expression, and Preventing Cellular Senescence, Evid.-Based Complement. Altern. Med. source

      Not checked in the free run.

    • cites [323] Rahimifard, M., Baeeri, M., Bahadar, H., Moini-Nodeh, S., Khalid, M., Haghi-Aminjan, H., Mohammadian, H., and Abdollahi, M. (2020). Therapeutic Effects of Gallic Acid in Regulating Senescence and Diabetes; an In Vitro Study. Molecules, 25. source

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    • cites [353] Guo, 2020, Gallic Acid Attenuates Thymic Involution in the D-Galactose Induced Accelerated Aging Mice, Immunobiology source

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  • May combine two claims.

    Premisecitation

    RSV can reduce oxidative damage in the brain of aged mice by increasing levels of SOD and plasma GPx, decreasing malondialdehyde, and lowering expression of pro-inflammatory proteins (IL1β and TNFα) in old mice, as well as in patients with coronary artery disease.

    “It has been demonstrated that RSV can reduce oxidative damage in the brain of aged mice by increasing the levels of SOD and plasma GPx, decreasing malondialdehyde, and lowering the expression of several pro-inflammatory proteins (IL1β and tumour necrosis factor α) in old mice, as well as in patients with coronary artery disease [321,322].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [321] Liu, 2012, Resveratrol Attenuates Oxidative Damage and Ameliorates Cognitive Impairment in the Brain of Senescence-Accelerated Mice, Life Sci. source

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    • cites [322] Tung, 2015, Anti-Inflammatory Effect of Resveratrol in Old Mice Liver, Exp. Gerontol. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Micronutrients (vitamins and minerals) are essential for human health and exert numerous functions including antioxidant defence.

    “Despite their tiny amount, micronutrients, i.e., vitamins and minerals, are essential for human health, exerting numerous functions, including antioxidant defence ranging from genome-related processes, such as DNA replication and repair, to metabolic processes and antioxidant defence [407,408].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [407] Shenkin, 2006, Micronutrients in Health and Disease, Postgrad. Med. J. source

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    • cites [408] Mehri, 2020, Trace Elements in Human Nutrition (II)—An Update, Int. J. Prev. Med. source

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  • May combine two claims.

    Premisecitation

    Zinc deficiency causes destabilization of membrane structure and increases oxidative stress.

    “In this respect, evidence showed that Zn deficiency causes destabilization of membrane structure and augments OS [424,425,426,427,428].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [424] Choi, 2018, Zinc Deficiency and Cellular Oxidative Stress: Prognostic Implications in Cardiovascular Diseases, Acta Pharmacol. Sin. source

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    • cites [425] Lee, 2018, Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems, Oxidative Med. Cell. Longev. source

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    • cites [426] Marreiro, D., Cruz, K., Morais, J., Beserra, J., Severo, J., and de Oliveira, A. (2017). Zinc and Oxidative Stress: Current Mechanisms. Antioxidants, 6. source

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    • cites [427] Yu, 2013, Zinc Oxide Nanoparticle Induced Autophagic Cell Death and Mitochondrial Damage via Reactive Oxygen Species Generation, Toxicol. Vitr. source

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    • cites [428] 2000, Role of Zinc in Plasma Membrane Function, J. Nutr. source

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  • May combine two claims.

    Premisecitation

    As an antioxidant agent, RSV can scavenge free radicals and reduce ROS formation by inhibiting expression of NADPH and glycogen synthase kinase 3 beta proteins, and upregulating expression of antioxidant enzymes such as SOD2, CAT, GPx, and thioredoxin.

    “As an antioxidant agent, RSV can scavenge free radicals and reduce ROS formation, by inhibiting the expression of NADPH and glycogen synthase kinase 3 beta proteins, and upregulating the expression of some antioxidant enzymes, such as SOD2, CAT, GPx, and thioredoxin [320,339,340].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [320] Liu, 2017, Resveratrol Protects against Oxidized Low-Density Lipoprotein-Induced Human Umbilical Vein Endothelial Cell Apoptosis via Inhibition of Mitochondrial-Derived Oxidative Stress, Mol. Med. Rep. source

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    • cites [339] Carrizzo, 2013, Antioxidant Effects of Resveratrol in Cardiovascular, Cerebral and Metabolic Diseases, Food Chem. Toxicol. source

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    • cites [340] Pagnussat, 2012, Resveratrol Prevents CA1 Neurons against Ischemic Injury by Parallel Modulation of Both GSK-3β and CREB through PI3-K/Akt Pathways, Eur. J. Neurosci. source

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  • May combine two claims.

    Premisecitation

    The Mediterranean Diet, which widely includes flavanols, flavanones, flavones and anthocyanins, is characterized by beneficial effects on health, including healthy aging as it hinders pathogenesis of many chronic diseases and extends life expectancy.

    “An indirect confirmation of this concept could be deduced by the fact that the Mediterranean Diet, which widely includes both flavanols, flavanones, flavons and anthocyanins, is characterized by well-known beneficial effects on health, including a healthy aging as it hinders the pathogenesis of many chronic diseases and extends life expectancy [317,318].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [317] Tosti, 2018, Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms, J. Gerontol. Ser. A source

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    • cites [318] Gantenbein, K.V., and Kanaka-Gantenbein, C. (2021). Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing. Nutrients, 13. source

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  • May combine two claims.

    Premisecitation

    Some studies have highlighted RSV's ability to also act as a pro-oxidant molecule, and this dual role depends upon cell type, used dosage, and exposure time.

    “Although RSV’s antioxidant properties have been widely demonstrated, some studies [349,350] have highlighted its ability to also act as a pro-oxidant molecule. This dual role depends upon cell type, used dosage, and exposure time [336].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [349] Kilic Eren, M., Kilincli, A., and Eren, Ö. (2015). Resveratrol Induced Premature Senescence Is Associated with DNA Damage Mediated SIRT1 and SIRT2 Down-Regulation. PLoS ONE, 10. source

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    • cites [350] Martins, 2014, Resveratrol Induces Pro-Oxidant Effects and Time-Dependent Resistance to Cytotoxicity in Activated Hepatic Stellate Cells, Cell Biochem. Biophys. source

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    • cites [336] Li, 2017, Resveratrol Sequentially Induces Replication and Oxidative Stresses to Drive P53-CXCR2 Mediated Cellular Senescence in Cancer Cells, Sci. Rep. source

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  • May combine two claims.

    Premisecitation

    CUR possesses antioxidant properties, through which it can prevent lipid peroxidation, stabilize Nrf2 with consequent expression of HO-1, and increase levels of antioxidant enzymes such as SOD, GST, GSH and GPx.

    “Further, CUR possesses antioxidant properties, through which it can prevent lipid peroxidation, stabilize Nrf2, with the consequent expression of HO-1, and increase the levels of antioxidant enzymes, such as SOD, GST, GSH and GPx [395].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [395] Zia, 2021, The Role of Curcumin in Aging and Senescence: Molecular Mechanisms, Biomed. Pharmacother. source

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  • May combine two claims.

    Premisecitation

    Lignans inhibit NADPH oxidase activity and upregulate antioxidant genes such as SOD1, SOD2, catalase, and DNA repairing genes.

    “In fact, they can suppress aging phenotypes in Drosophila adults, inhibit NADPH oxidase activity and upregulate antioxidant genes, such as SOD1, SOD2, catalase, and DNA repairing genes [221,404].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [221] Yu, 2010, Oxidative Stress with an Activation of the Renin-Angiotensin System in Human Vascular Endothelial Cells as a Novel Mechanism of Uric Acid-Induced Endothelial Dysfunction, J. Hypertens source

      Not checked in the free run.

    • cites [404] Le, 2019, Sesamin Suppresses Aging Phenotypes in Adult Muscular and Nervous Systems and Intestines in a Drosophila Senescence-Accelerated Model, Eur. Rev. Med. Pharm. Sci.

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  • May combine two claims.

    Premisecitation

    Treatment with p-CA promotes expression of Nrf2, with consequent increased levels of antioxidant enzymes including HO-1, SOD, NAD(P)H quinone dehydrogenase 1, CAT, and GPx.

    “Being an antioxidant agent, the treatment with this acid promotes the expression of Nrf2, with the consequent increased levels of some antioxidant enzymes, including HO-1, SOD, NAD(P)H quinone dehydrogenase 1, CAT, and GPx [328].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [328] Shen, 2019, Protective Effects of P-Coumaric Acid against Oxidant and Hyperlipidemia-an in Vitro and in Vivo Evaluation, Biomed. Pharmacother. source

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  • May combine two claims.

    Premisecitation

    As an antioxidant agent, EA can activate cellular antioxidant enzymes like SOD, CAT and GPx, protect DNA from ROS and chelate metal ions.

    “As an antioxidant agent, EA can activate cellular antioxidant enzymes, like SOD, CAT and GPx, protect DNA from ROS and chelate metal ions [365].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [365] Baeeri, 2017, Molecular Evidence on the Protective Effect of Ellagic Acid on Phosalone-Induced Senescence in Rat Embryonic Fibroblast Cells, Food Chem. Toxicol. source

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  • May combine two claims.

    Premisecitation

    FA has been shown to prevent type 2 diabetes and AD by regulating antioxidant enzymes and caspase activities.

    “Thanks to its antioxidants, anti-diabetic, and neuroprotective properties [373,374], it has been shown to prevent type 2 diabetes and AD [375,376] by regulating antioxidant enzymes and caspase activities [326].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [375] Meng, 2018, Application of Ferulic Acid for Alzheimer’s Disease: Combination of Text Mining and Experimental Validation, Front. Neuroinform. source

      Not checked in the free run.

    • cites [376] Narasimhan, 2015, Ferulic Acid Exerts Its Antidiabetic Effect by Modulating Insulin-Signalling Molecules in the Liver of High-Fat Diet and Fructose-Induced Type-2 Diabetic Adult Male Rat, Appl. Physiol. Nutr. Metab. source

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    • cites [326] Hahn, 2016, Pretreatment of Ferulic Acid Protects Human Dermal Fibroblasts against Ultraviolet A Irradiation, Ann. Dermatol. source

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  • May combine two claims.

    Premisecitation

    Anthocyanins contrast senescence by promoting neural stem cell proliferation and diminishing aging-related markers and cognitive impairment in mice.

    “It has been reported that anthocyanins contrast senescence as they promote neural stem cells proliferation and diminish aging-related markers and cognitive impairment in mice [313].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [313] Gao, 2020, Anti-Aging Effects of Ribes Meyeri Anthocyanins on Neural Stem Cells and Aging Mice, Aging source

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  • May combine two claims.

    Premisecitation

    Manganese supplementation might improve antioxidant functions in the lungs and ameliorate asthma conditions.

    “Despite some controversial data arise, other findings point out that Mn supplementation might improve antioxidant functions in the lungs and ameliorate asthma conditions, as reported in a recent review [449].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [449] Zajac, D. (2021). Mineral Micronutrients in Asthma. Nutrients, 13. source

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  • May combine two claims.

    Premisecitation

    Zinc-finger protein 768 is overexpressed in cancer cells, contributing to cell proliferation and repressing senescence.

    “Again, the Zn-finger protein 768 has been found to be overexpressed in cancer cells, contributing to cell proliferation and repressing senescence [437].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [437] Poirier, A., Gagné, A., Laflamme, P., Marcoux, M., Orain, M., Plante, S., Joubert, D., Joubert, P., and Laplante, M. (2021). ZNF768 Expression Associates with High Proliferative Clinicopathological Features in Lung Adenocarcinoma. Cancers, 13. source

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  • May combine two claims.

    Premisecitation

    In magnesium-deficient embryo-hepatocytes, production of hydrogen peroxide and oxidative damage are enhanced.

    “Further, an enhanced production of hydrogenase peroxide and oxidative damage were measured in Mg-deficient embryo-hepatocytes [418].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [418] Yang, 2006, Magnesium Deficiency Enhances Hydrogen Peroxide Production and Oxidative Damage in Chick Embryo Hepatocyte In Vitro, BioMetals source

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  • May combine two claims.

    Premisecitation

    In vitro, zinc deficiency is associated with increased ROS production, oxidative damage to DNA, proteins, and lipids, membrane destabilization, and dysregulation of metallothionein.

    “In vitro studies have shown that Zn deficiency is associated with an increased production of ROS, oxidative damage to DNA, proteins and lipids, destabilization of membrane structure, dysregulation of Zn-binding protein metallothionein [426,429].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [426] Marreiro, D., Cruz, K., Morais, J., Beserra, J., Severo, J., and de Oliveira, A. (2017). Zinc and Oxidative Stress: Current Mechanisms. Antioxidants, 6. source

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    • cites [429] Eide, 2011, The Oxidative Stress of Zinc Deficiency, Metallomics source

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  • May combine two claims.

    Premisecitation

    Magnesium has structural roles in DNA, proteins, and enzymes including telomerases, and promotes DNA replication, transcription, protein synthesis, and mitochondrial functions.

    “Magnesium has structural roles in DNA, proteins and enzymes including telomerases. It promotes DNA replication and transcription, protein synthesis and mitochondrial functions [444,445].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [444] Hartwig, 2001, Role of Magnesium in Genomic Stability, Mutat. Res./Fundam. Mol. Mech. Mutagenesis source

      Not checked in the free run.

    • cites [445] Maguire, D., Neytchev, O., Talwar, D., McMillan, D., and Shiels, P. (2018). Telomere Homeostasis: Interplay with Magnesium. Int. J. Mol. Sci., 19. source

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  • May combine two claims.

    Premisecitation

    Cells deficient in Selenoprotein H display high oxidative stress, persistent DNA damage, and decreased glutathione.

    “In support of this concept, cells deficient in Selenoprotein H (a nuclear protein) displayed high levels of OS, persistent DNA damage and a decreased content in antioxidant molecules (glutathione) [414].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [414] Wu, 2014, Selenoprotein H Suppresses Cellular Senescence through Genome Maintenance and Redox Regulation, J. Biol. Chem. source

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  • May combine two claims.

    Premisecitation

    Thioredoxin reductases contribute to regulation of gene expression of transcription factors implicated in inflammatory and cell cycle pathways, and in recycling of antioxidant molecules.

    “A second crucial family of proteins containing SeCys and involved in redox biology is thioredoxin reductases (TRs), which contribute to the regulation of gene expression of multiple transcription factors implicated in inflammatory and cell cycle pathways (e.g., NF-kB and p53) [442], as well as in the recycling of antioxidant molecules [441].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [442] Selenius, 2010, Selenium and the Selenoprotein Thioredoxin Reductase in the Prevention, Treatment and Diagnostics of Cancer, Antioxid. Redox Signal. source

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    • cites [441] Hariharan, 2020, Selenium and Selenoproteins: It’s Role in Regulation of Inflammation, Inflammopharmacology source

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  • May combine two claims.

    Premisecitation

    In animals, a long-term magnesium-deficient diet disrupts redox balance and homeostasis, increases inflammation, and exacerbates development and progression of aging-related diseases such as cardiovascular diseases, hypertension, and diabetes.

    “Accordingly, animal studies have confirmed that a long-term Mg-deficient diet disrupts the redox balance and homeostasis and increases inflammation, consequently exacerbating the development and progression of aging-related diseases such as cardiovascular diseases, hypertension, or diabetes [420,446].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [420] Blache, 2006, Long-Term Moderate Magnesium-Deficient Diet Shows Relationships between Blood Pressure, Inflammation and Oxidant Stress Defense in Aging Rats, Free Radic. Biol. Med. source

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    • cites [446] Mazur, 2007, Magnesium and the Inflammatory Response: Potential Physiopathological Implications, Arch. Biochem. Biophys. source

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  • May combine two claims.

    Premisecitation

    In vitro, selenium supplementation reduces ROS levels, DNA damage, telomere shortening, and senescence biomarkers in bone marrow stromal cells, cultured human fibroblasts, and keratinocytes.

    “For instance, in bone marrow stromal cells [443], cultured human fibroblasts [412], and keratinocytes [413], Se supplementation reduces ROS levels, DNA damage, telomere shortening and senescence biomarkers.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [443] Ebert, 2006, Selenium Supplementation Restores the Antioxidative Capacity and Prevents Cell Damage in Bone Marrow Stromal Cells In Vitro, Stem cells source

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    • cites [412] Legrain, 2014, Interplay between Selenium Levels, Selenoprotein Expression, and Replicative Senescence in WI-38 Human Fibroblasts, J. Biol. Chem. source

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    • cites [413] Jobeili, 2017, Selenium Preserves Keratinocyte Stemness and Delays Senescence by Maintaining Epidermal Adhesion, Aging source

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  • May combine two claims.

    Premisecitation

    Melatonin's antioxidant and anti-inflammatory activities are exerted through suppression of COX-2, NLRP3 inflammasome, gasdermin D, TLR-4, NF-kB, and NO release, and activation of SIRT1 and Nrf2.

    “Its antioxidant and anti-inflammatory activities are exerted through the suppression of cyclooxygenase 2, NLRP3 inflammasome, gasdermin D, TLR-4, NF-kB, and NO release, as well as the concomitant activation of SIRT1 and Nrf2 free radical scavenging network [452].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [452] Hardeland, R. (2019). Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks. Int. J. Mol. Sci., 20. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Human fibroblasts cultured in magnesium-deficient conditions show rapid telomere shortening and decreased replicative lifespan.

    “Additionally, human fibroblasts cultured in Mg-deficient conditions showed a rapid telomere shortening and a decreased replicative lifespan [419].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [419] Killilea, 2008, Magnesium Deficiency Accelerates Cellular Senescence in Cultured Human Fibroblasts, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In endothelial cell cultures, magnesium deficiency enhances free radical production and cell apoptosis, and increases release of pro-inflammatory molecules.

    “Cell culture studies have demonstrated that Mg shortage negatively impact antioxidant defence, cell cycle progression and cellular viability; in particular, its deficiency in endothelial cell cultures enhances free radicals production and cell apoptosis [416], and increases the release of pro-inflammatory molecules [417].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [416] Dickens, 1992, Magnesium Deficiency in Vitro Enhances Free Radical-Induced Intracellular Oxidation and Cytotoxicity in Endothelial Cells, FEBS Lett. source

      Not checked in the free run.

    • cites [417] Wolf, 2008, Magnesium Deficiency and Endothelial Dysfunction: Is Oxidative Stress Involved?, Magnes Res.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Melatonin is a hormone produced and released by the pineal gland with immunomodulatory, oncostatic, anti-aging, and endocrine modulator functions.

    “Melatonin is a hormone produced and released by the pineal gland with immunomodulatory, oncostatic, anti-aging, and endocrine modulator functions [450,451].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [450] Majidinia, 2018, The Role of Melatonin, a Multitasking Molecule, in Retarding the Processes of Ageing, Ageing Res. Rev. source

      Not checked in the free run.

    • cites [451] Lahiri, 1999, Interactions between Melatonin, Reactive Oxygen Species, and Nitric Oxide, Ann. N. Y. Acad. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Melatonin decreases p53, p21, and p16 proteins and enhances SIRT1 activity in H2O2-induced senescence.

    “Melatonin-induced decrease in p53, p21 and p16 proteins, together with enhanced SIRT1 activity, have also been reported in the context of H2O2-induced senescence [458,459].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [458] Cai, 2016, Long Noncoding RNA H19 Mediates Melatonin Inhibition of Premature Senescence of C-Kit+ Cardiac Progenitor Cells by Promoting MiR-675, J. Pineal Res. source

      Not checked in the free run.

    • cites [459] Zhou, 2015, Melatonin Reverses H2O2-Induced Premature Senescence in Mesenchymal Stem Cells via the SIRT1-Dependent Pathway, J. Pineal Res. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Genetic factors account for 25% to 30% of life expectancy.

    “It was shown that less calories [469], good sleep [470], less stress [471], good relationships [472], no smoke and low alcohol drinking are environmental factors capable of delaying aging, while genetic factors play a role for in 25% to 30% of life expectancy [473].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [473] Young, 2018, Validated Living Worldwide Supercentenarians, Living and Recently Deceased: February 2018, Rejuvenation Res. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    ROS are fundamentally signalling molecules and most stress responding mechanisms are tuned by fine modulation of ROS as signalling agents.

    “Aging is usually considered as a major playground of oxidative stress, but it should be highlighted that ROS are fundamentally signalling molecules and that most of the stress responding mechanisms are tuned by fine modulation of ROS as signalling agents.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In vivo, melatonin intake diminishes age-derived inflammation and apoptosis, decreases lipid peroxidation, TBARS, and protein carbonyls, counteracting hippocampal senescence and exerting anti-aging and antioxidant effects on mice brains.

    “In vivo, melatonin intake has been reported to diminish age-derived inflammation and apoptosis and to decrease lipid peroxidation, thiobarbituric acid reactive substances and protein carbonyls, thus counteracting hippocampal senescence and exerting an anti-aging and antioxidant effect on mice brains [462,463,464,465].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [462] Puig, 2016, Melatonin Decreases the Expression of Inflammation and Apoptosis Markers in the Lung of a Senescence-Accelerated Mice Model, Exp. Gerontol. source

      Not checked in the free run.

    • cites [463] Parisotto, 2016, Chronic Melatonin Administration Reduced Oxidative Damage and Cellular Senescence in the Hippocampus of a Mouse Model of Down Syndrome, Neurochem. Res. source

      Not checked in the free run.

    • cites [464] Okatani, 2002, Melatonin Reduces Oxidative Damage of Neural Lipids and Proteins in Senescence-Accelerated Mouse, Neurobiol. Aging source

      Not checked in the free run.

    • cites [465] Sumsuzzman, 2021, Differential Role of Melatonin in Healthy Brain Aging: A Systematic Review and Meta-Analysis of the SAMP8 Model, Aging source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In vascular demented rats, melatonin treatment ameliorates brain oxidative stress and increases osteopontin and senescence marker protein-30.

    “Finally, brain oxidative stress amelioration and increased osteopontin and senescence marker protein-30 have been shown following melatonin treatment in the context of vascular demented rats [466].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [466] Sakr, 2018, Melatonin Ameliorates Brain Oxidative Stress and Upregulates Senescence Marker Protein-30 and Osteopontin in a Rat Model of Vascular Dementia, Physiol. Int. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Melatonin supplementation decreases cellular senescence, preserves self-renewal, and activates antioxidant defence pathways in MSCs.

    “In this context, decreased cellular senescence, preserved self-renewal and activation of antioxidant defence pathways have all been observed after melatonin supplementation [460,461].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [460] Liao, 2019, Antioxidants Inhibit Cell Senescence and Preserve Stemness of Adipose Tissue-Derived Stem Cells by Reducing ROS Generation during Long-Term In Vitro Expansion, Stem Cell Res. Ther. source

      Not checked in the free run.

    • cites [461] Shuai, 2016, Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-Term In Vitro Expansion, Theranostics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Melatonin can stimulate release of pro-inflammatory factors depending on concurrent conditions, with response limited to early treatment stages.

    “However, melatonin can also stimulate the release of pro-inflammatory factors depending on the concurrent conditions, although this response seems to be limited to early treatment stages and needs to be better investigated [454].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [454] Radogna, 2010, Melatonin: A Pleiotropic Molecule Regulating Inflammation, Biochem. Pharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Melatonin treatment inhibits sodium nitroprusside-mediated NO release in neuroblastoma cells and increases transcripts for SOD1, GPx1, and CAT in HUVEC.

    “For example, inhibition of sodium nitroprusside-mediated NO release and increased production of transcripts coding for antioxidant enzymes (i.e., SOD1, GPx1 and CAT) have been reported upon melatonin treatment in neuroblastoma cells and HUVEC, respectively [451,453].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [451] Lahiri, 1999, Interactions between Melatonin, Reactive Oxygen Species, and Nitric Oxide, Ann. N. Y. Acad. Sci. source

      Not checked in the free run.

    • cites [453] Huang, 2020, Melatonin Prevents Endothelial Dysfunction in SLE by Activating the Nuclear Receptor Retinoic Acid-Related Orphan Receptor-α, Int. Immunopharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Long-term culture of MSCs stimulates ROS generation, promoting oxidative stress-induced senescence.

    “Regarding MSCs, it is known that long term culture stimulates ROS generation, thus promoting oxidative stress-induced senescence [460].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [460] Liao, 2019, Antioxidants Inhibit Cell Senescence and Preserve Stemness of Adipose Tissue-Derived Stem Cells by Reducing ROS Generation during Long-Term In Vitro Expansion, Stem Cell Res. Ther. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Melatonin reduces oxidative stress and replicative senescence by enhancing autophagy, activating AMPK/FOXO3 pathways, and increasing mitochondrial membrane potential, both in vitro and in vivo.

    “In this respect, melatonin has been proven capable of reducing oxidative stress and replicative senescence by enhancing autophagy, activating AMPK/FOXO3 pathways and increasing mitochondrial membrane potential, both in vitro and in vivo [455,456,457].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [455] Lee, 2020, Melatonin Suppresses Senescence-derived Mitochondrial Dysfunction in Mesenchymal Stem Cells via the HSPA1L–Mitophagy Pathway, Aging Cell source

      Not checked in the free run.

    • cites [456] Chen, 2021, Anti-Apoptosis and Autophagy Effects of Melatonin Protect Rat Chondrocytes against Oxidative Stress via Regulation of AMPK/Foxo3 Pathways, CARTILAGE source

      Not checked in the free run.

    • cites [457] Wu, K.K. (2021). Control of Mesenchymal Stromal Cell Senescence by Tryptophan Metabolites. Int. J. Mol. Sci., 22. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Aging is a risk factor for chronic diseases, atherosclerosis, cardiovascular diseases, stroke, kidney failure, chronic lung disease, cancers, diabetes, osteoporosis, arthritis, blindness, dementia, and neurodegenerative diseases.

    “Aging is one of the risk factors for chronic diseases, atherosclerosis, cardiovascular diseases, stroke, kidney failure, chronic lung disease, cancers, diabetes, osteoporosis, arthritis, blindness, dementia, and neurodegenerative diseases [467,468].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [467] Singh, 2019, The Genetics of Aging: A Vertebrate Perspective, Cell source

      Not checked in the free run.

    • cites [468] Blasco, 2013, The Hallmarks of Aging, Cell source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Environmental factors such as fewer calories, good sleep, less stress, good relationships, no smoking, and low alcohol drinking can delay aging.

    “It was shown that less calories [469], good sleep [470], less stress [471], good relationships [472], no smoke and low alcohol drinking are environmental factors capable of delaying aging, while genetic factors play a role for in 25% to 30% of life expectancy [473].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [469] Redman, 2018, Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging, Cell Metab. source

      Not checked in the free run.

    • cites [470] Mazzotti, 2014, Human Longevity Is Associated with Regular Sleep Patterns, Maintenance of Slow Wave Sleep, and Favorable Lipid Profile, Front. Aging Neurosci. source

      Not checked in the free run.

    • cites [471] Epel, 2014, Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity, J. Gerontol. Ser. A Biol. Sci. Med. Sci. source

      Not checked in the free run.

    • cites [472] Jenkinson, C.E., Dickens, A.P., Jones, K., Thompson-Coon, J., Taylor, R.S., Rogers, M., Bambra, C.L., Lang, I., and Richards, S.H. (2013). Is Volunteering a Public Health Intervention? A Systematic Review and Meta-Analysis of the Health and Survival of Volunteers. BMC Public Health, 13. source

      Not checked in the free run.

108 of 108

  • The paper relies on this without support.

    A comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking.

    “However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking.”
    “Despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking.”

  • The paper relies on this without support.

    Most studies investigated a single compound on a particular cell line or specific animal model, which often prevents generalizing results to a broader context.

    “Currently this remains a limit, as most of the studies investigated a single compound on a particular cell line or on a specific animal model, which often prevents generalizing the results in a broader context.”

  • The paper relies on this without support.

    There are still few studies on the synergy and interference of multiple antioxidants taken in combination.

    “There are still few studies on the synergy and interference of multiple antioxidants taken in combination—increasingly fashionable in the modern society—and the benefits and risks of this approach should be carefully evaluated.”

  • The paper relies on this without support.

    It is difficult to indicate if an antioxidant vitamin is senolytic or senomorphic.

    “It is difficult, to date, to indicate if an anti-oxidant vitamin is senolytic or senomorphic, due to the huge complexity of biological phenomena.”

  • The paper relies on this without support.

    Time of initiation and duration of antioxidant treatment might affect clinical outcomes.

    “From a human perspective, not only dose assessment but also the time of initiation (childhood, adolescence, adulthood, old age) and the duration of the treatment (lifelong, at alternating intervals or for a defined period) might affect the clinical outcomes.”

  • The paper relies on this without support.

    Effects of antioxidant supplements may depend on time of day and individual differences such as physical activity and lifestyle.

    “Similarly, when integrated as supplements, antioxidants may give rise to different effects depending upon the time of the day they are taken and individual differences such as physical activity and lifestyle, which may also greatly vary among subjects.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

2 retracted

Flagged first, then by citations

Research works printed but not linked: 4

  1. Emmanuele, 2012, Heterogeneity of Coenzyme Q10 Deficiency: Patient study and literature review, Arch. Neurol., 69, 978, 10.1001/archneurol.2012.206 · DOI · Paper page
  2. Reifen, 2017, Vitamin A and the Epigenome, Crit. Rev. Food Sci. Nutr., 57, 2404, 10.1080/10408398.2015.1060940 · DOI
  3. Ross, A.C., Caballero, B.H., Cousins, R.J., Tucker, K.L., and Ziegler, T.R. (2012). Modern Nutrition in Health and Disease, Wolters Kluwer Health Adis (ESP). [11th ed.].
  4. Singh, 2022, Fisetin, a Potential Caloric Restriction Mimetic, Modulates Ionic Homeostasis in Senescence Induced and Naturally Aged Rats, Arch. Physiol. Biochem., 128, 51, 10.1080/13813455.2019.1662452 · DOI

Cited by

Sorted by citations

Authors
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A.
Affiliations
  • University of Pavia (IT)
  • University of Verona (IT)
  • University of Lancashire (GB)
  • Université Libre de Bruxelles (BE)
  • Centro San Giovanni di Dio Fatebenefratelli (IT)
Corresponding author
  • Varesi, Angelica
  • Pascale, Alessia
ORCID
Venue
Antioxidants
Publisher
MDPI AG
Published
2022-06-22
Volume
11
Issue
7
Pages
1224
ISSN
2076-3921 (ISSN-L)
DOI
10.3390/antiox11071224
PMC
PMC9311946
OpenAlex
W4283318547
Cited by
145
References
477
Citations by year
2026: 31 · 2025: 36 · 2024: 44 · 2023: 28 · 2022: 6
FWCI
3.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Antioxidants (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CLOK (University of Central Lancashire) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • IrInSubria (University of Insubria) (submittedVersion, other-oa)
Funders
the Italian Ministry of Health as Ricerca Corrente (RF-2016-02363298)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
cellular senescence, oxidative stress, aging, reactive oxygen species, telomere shortening, DNA damage, vitamins, carotenoids, organosulfur compounds, flavonoids, minerals, lifespan extension, anti-aging compounds

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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