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Oxidative stress–linked DNA damage, mutations, and epigenetic modifications influence tumor initiation, angiogenesis, metastasis, and resistance to 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 \nEmma Di Carlo 1,2, * and Carlo Sorrentino 1,2  \nCitation: Di Carlo, E.; Sorrentino, C. Oxidative Stress and Age-Related Tumors. Antioxidants 2024, 13, 1109 .  \n[https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)antiox13091109  \nAcademic Editor: Alessandra Napolitano  \nReceived: 19 July 2024  \nRevised: 6 September 2024  \nAccepted: 10 September 2024  \nPublished: 13 September 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Medicine and Sciences of Aging,“G. d’Annunzio” University of Chieti-Pescara,  \n66100 Chieti, Italy  \n2 Anatomic Pathology and Immuno-Oncology Unit, Center for Advanced Studies and Technology (CAST),“G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy  \n* Correspondence: [edicarlo@unich.it](edicarlo@unich.it); Tel.: +39-0871-541540  \nAbstract: Oxidative stress is the result of the imbalance between reactive oxygen and nitrogen species (RONS), which are produced by several endogenous and exogenous processes, and antioxidant defenses consisting of exogenous and endogenous molecules that protect biological systems from free radical toxicity. Oxidative stress is a major factor in the aging process, contributing to the accumulation of cellular damage over time. Oxidative damage to cellular biomolecules, leads to DNA alterations, lipid peroxidation, protein oxidation, and mitochondrial dysfunction resulting in cellular senescence, immune system and tissue dysfunctions, and increased susceptibility to age-related pathologies, such as inflammatory disorders, cardiovascular and neurodegenerative diseases, diabetes, and cancer. Oxidative stress-driven DNA damage and mutations, or methylation and histone modification, which alter gene expression, are key determinants of tumor initiation, angiogenesis, metastasis, and therapy resistance. Accumulation of genetic and epigenetic damage, to which oxidative stress contributes, eventually leads to unrestrained cell proliferation, the inhibition of cell differentiation, and the evasion of cell death, providing favorable conditions for tumorigenesis. Colorectal, breast, lung, prostate, and skin cancers are the most frequent aging-associated malignancies, and oxidative stress is implicated in their pathogenesis and biological behavior. Our aim is to shed light on the molecular and cellular mechanisms that link oxidative stress, aging, and cancers, highlighting the impact of both RONS and antioxidants, provided by diet and exercise, on cellular senescence, immunity, and development of an antitumor response. The dual role of ROS as physiological regulators of cell signaling responsible for cell damage and diseases, as well as its use for anti-tumor therapeutic purposes, will also be discussed. Managing oxidative stress is crucial for promoting healthy aging and reducing the risk of age-related tumors.  \nKeywords: oxidative stress; cancer; aging; antioxidants  \n1. Introduction  \nOxidative stress is implicated in numerous physiological processes, including cell signaling, immune response, and the regulation of gene expression [1] . In normal conditions, the production of reactive oxygen species (ROS), such as the hydroxyl radical (•OH), the superoxide anion (O 2•− ), hydrogen peroxide (H 2O2 ), singlet oxygen (1O2 ), and reactive nitrogen species (RNS, generated when nitric oxide interacts with reactive oxygen species) [2], such as nitric oxide (NO), and peroxynitrite (ONOO − ), normally generated as by-products of the oxygen and nitrogen metabolism, is balanced by the presence of antioxidants, such as superoxide dismutase (SOD), glutathione, glutathi","cbCaiaO1F8wP9nvm","https://ap.wps.com/l/cbCaiaO1F8wP9nvm","pdf",3249832,32,"English","# Abstract\n# Introduction\n## Oxidative stress, redox homeostasis, and RONS\n## Oxidative distress, aging, and inflammaging\n# Antioxidant and Oxidative Stress Driving Genes","[{\"question\":\"What causes oxidative stress in biological systems?\",\"answer\":\"Oxidative stress results from an imbalance between reactive oxygen and nitrogen species (RONS) produced by endogenous and exogenous processes and antioxidant defenses made by exogenous and endogenous molecules.\"},{\"question\":\"How does oxidative stress contribute to aging and age-related diseases?\",\"answer\":\"It drives accumulation of damage to DNA, lipids, proteins, and mitochondria, leading to cellular senescence, immune and tissue dysfunction, and increased susceptibility to conditions such as inflammatory disorders, cardiovascular and neurodegenerative diseases, diabetes, and cancer.\"},{\"question\":\"How is oxidative stress linked to tumor development and treatment resistance?\",\"answer\":\"Oxidative stress–driven DNA damage and mutations, together with methylation and histone modifications that alter gene expression, influence tumor initiation, angiogenesis, metastasis, and therapy resistance.\"}]","Oxidative Stress and Age-Related Tumors - Antioxidants Review | PDF",1790016569,81]