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

Angelica Varesi, Salvatore Chirumbolo, Lucrezia Irene Maria Campagnoli, Elisa Pierella, Gaia Bavestrello Piccini, Adelaide Carrara, Giovanni Ricevuti, Catia Scassellati, Cristian Bonvicini, Alessia Pascale, Angelica Varesi, Salvatore Chirumbolo, Lucrezia Irene Maria Campagnoli, Elisa Pierella, Gaia Bavestrello Piccini, Adelaide Carrara, Giovanni Ricevuti, Catia Scassellati, Cristian Bonvicini, Alessia Pascale

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.

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.

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