Antioxidant Strategies Against Cellular Senescence: Unveiling the Power of Synthetic Versus Natural Antioxidants in a Systematic Review

Farbod Ebrahimirad¹Seyedeh Elahe Mirmahdizade²Bahar Mahmoodieh³Saina Najafi¹Seyedeh Marzieh Banihashemian⁴Sadegh Nikakhtar⁵Asma Sadeghi⁶Naghmeh Kossari⁷Seyyed Kiarash Sadat RAfiei⁸Masood Ghodsi Moghadam⁹Mahsa Asadi Anar^10*

• ¹Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
• ²Department of Food Science and Technology, Science and Research Branch, Islamic Azad University, Tehran, Iran
• ³School of Medicine, Iran University of Medical Sciences, Tehran, Iran
• ⁴School of Advanced Sciences and Technology, Tehran Medical Branch, Islamic Azad University, Tehran, Alborz, Iran
• ⁵Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Alborz, Iran
• ⁶Department of Food Science and Technology, Faculty of Agriculture, University of Tabriz, Tabriz, Iran
• ⁷Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
• ⁸School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
• ⁹Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
• ¹⁰College of Medicine, University of Arizona, Tucson, Arizona, United States

Background: Cellular senescence, characterized by irreversible cell cycle arrest, plays a pivotal role in ageing and the development of age-related pathologies. Mitigating oxidative stress, a primary contributor to cellular ageing, is crucial for inhibiting the senescence-associated secretory phenotype (SASP). A comparative analysis of synthetic and natural antioxidants is necessary to evaluate the efficacy of synthetic and natural antioxidants in this context.A systematic review encompassed studies published up to July 2023, utilizing prominent databases such as PubMed, Google Scholar, Scopus, and Web of Science. To enhance the efficiency of data screening and selection, we employed Rayyan.ai, an advanced tool designed for systematic reviews.The review encompassed 33 studies examining the impact of diverse antioxidants on cellular senescence. Findings indicated that synthetic antioxidants, such as N-acetylcysteine, and natural alternatives, like Vitamin C, demonstrated efficacy in attenuating oxidative stress and senescence markers. Notably, natural antioxidants frequently exhibited comparable or superior efficacy to their synthetic counterparts in most studies. Furthermore, the synergistic effects of antioxidant combinations sometimes yield enhanced benefits. It is worth noting that certain recently developed synthetic compounds, such as MHY2233, have shown promising results, exhibiting greater potency than established antioxidants in mitigating senescence markers.Dietary practices and the aging process can influence these intricate processes and how they interact, serving as potential primary and secondary preventative strategies. The Mediterranean diet, dietary antioxidants, and limiting calorie intake are promising nutritional strategies. Better insight into the molecular mechanisms of aging may facilitate the development of efficient biomarkers and antioxidants for diagnosis or treatment.