Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun 22;11(7):1224.
doi: 10.3390/antiox11071224.

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

Angelica Varesi  1   2 , Salvatore Chirumbolo  3 , Lucrezia Irene Maria Campagnoli  4 , Elisa Pierella  5 , Gaia Bavestrello Piccini  6 , Adelaide Carrara  7 , Giovanni Ricevuti  8 , Catia Scassellati  9 , Cristian Bonvicini  10 , Alessia Pascale  4
Affiliations
Review

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

Angelica Varesi et al. Antioxidants (Basel). .

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.

Keywords: aging; antioxidants; flavonoids; minerals; oxidative stress; reactive oxygen species; senescence; vitamins.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The interplay between oxidative stress (OS) and senescence. Excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) trigger senescence through different mechanisms: (i) via NF-kB stimulation, which induces the transcription of the main factors composing the senescence-associated secretory phenotype (SASP); (ii) through DNA double strand brakes, which trigger a sustained DDR response; (iii) via telomere shortening, which is directly linked to cellular senescence; (iv) through a double cross-talk between mitochondria dysfunction and ROS/RNS production and (v) via the inhibition of Nrf2, a crucial antioxidant transcription factor. Antioxidant molecules and antioxidant enzymes (i.e., superoxide dismutase, catalase and glutathione peroxidase) can counteract senescence through the inhibition of OS. Abbreviations: ARE: antioxidant responsive element; CAT: catalase; DDR: DNA damage response; GCL: glutamate cysteine ligase; GPx: glutathione peroxidase; GST: glutathione transferase; H2O2: hydrogen peroxide; HO-1: heme oxygenase-1; HO•: hydroxyl radical; HOO•: hydroperoxyl radical; IL-1β: interleukin 1β; NF-kB: nuclear factor kappa-light-chain-enhancer of activated B cells; NO•: nitric oxide radical; NO2•: nitrogen dioxide radical; NQO1: NAD(P)H quinone dehydrogenase 1; Nrf2: nuclear factor erythroid 2-related factor 2; O2•−: superoxide anion radical; ONOO−: peroxynitrite anion radical; PST: phenolsulfotransferase enzyme; SOD: superoxide dismutase; TNF-α: tumour necrosis factor α.
Figure 2
Figure 2
Antioxidants: classification. The figure illustrates the main classes of antioxidants capable of counteracting oxidative stress-induced senescence: enzymes, mitochondria-targeted antioxidants, vitamins, carotenoids, organosulfur compounds, nitrogen non protein compounds, flavonoids, minerals, non-flavonoids, and others.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hayflick L., Moorhead P.S. The Serial Cultivation of Human Diploid Cell Strains. Exp. Cell Res. 1961;25:585–621. doi: 10.1016/0014-4827(61)90192-6. - DOI - PubMed
    1. Calcinotto A., Kohli J., Zagato E., Pellegrini L., Demaria M., Alimonti A. Cellular Senescence: Aging, Cancer, and Injury. Physiol. Rev. 2019;99:1047–1078. doi: 10.1152/physrev.00020.2018. - DOI - PubMed
    1. Gorgoulis V., Adams P.D., Alimonti A., Bennett D.C., Bischof O., Bishop C., Campisi J., Collado M., Evangelou K., Ferbeyre G., et al. Cellular Senescence: Defining a Path Forward. Cell. 2019;179:813–827. doi: 10.1016/j.cell.2019.10.005. - DOI - PubMed
    1. di Micco R., Krizhanovsky V., Baker D., d’Adda di Fagagna F. Cellular Senescence in Ageing: From Mechanisms to Therapeutic Opportunities. Nat. Rev. Mol. Cell Biol. 2021;22:75–95. doi: 10.1038/s41580-020-00314-w. - DOI - PMC - PubMed
    1. Krizhanovsky V., Yon M., Dickins R.A., Hearn S., Simon J., Miething C., Yee H., Zender L., Lowe S.W. Senescence of Activated Stellate Cells Limits Liver Fibrosis. Cell. 2008;134:657–667. doi: 10.1016/j.cell.2008.06.049. - DOI - PMC - PubMed

Grants and funding

This research was supported by grants from the Italian Ministry of Health as Ricerca Corrente and as RF-2016-02363298.

LinkOut - more resources