• Harnessing the fundamental roles of vitamins: the potent anti‑oxidants in longevity
  • Mehran Izadi,1 Nariman Sadri,2 Amirhossein Abdi,3 Mohammad Mahdi Raeis zadeh,4 Ghazalnaz Baghdadi,5 Safa Tahmasebi,6,*
    1. Department of Infectious and Tropical Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
    2. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    3. School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
    4. School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
    5. Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
    6. Student Research Committee, Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


  • Introduction: Introduction: Aging is a complex biological process characterized by a progressive decline in physiological integrity, leading to impaired function and increased susceptibility to diseases such as cancer, metabolic disorders, and neurodegeneration. The hallmarks of aging—including genomic instability, telomere attrition, mitochondrial dysfunction, and cellular senescence—are interconnected and contribute to this decline. Nutritional interventions, particularly vitamins, have emerged as potent modulators of these pathways, extending beyond their classical roles in preventing deficiency diseases. This review synthesizes current evidence on the fundamental roles of vitamins as antioxidants and hormetic agents that can activate protective cellular stress responses, repair mechanisms, and homeostatic processes, thereby promoting longevity and healthy aging.
  • Methods: Methods: This comprehensive review analyzes and synthesizes findings from a wide array of preclinical studies, epidemiological research, and human randomized controlled trials (RCTs) investigating the relationship between vitamin intake—both dietary and supplemental—and the biological mechanisms of aging. The examined evidence encompasses studies on vitamins' roles in modulating epigenetic clocks (e.g., DNA methylation age), oxidative stress, the IGF-1 signaling pathway, cellular senescence, chronic inflammation ("inflammaging"), stem cell exhaustion, and immune system function. The methodological approach involved a critical evaluation of the consistency, mechanisms, and clinical applicability of the reported effects across different study models and populations.
  • Results: Results: The analysis reveals that vitamins exert significant influence on key aging mechanisms through diverse pathways. Vitamins such as B9 (folate) and B12 were shown to decelerate the epigenetic clock, though their efficacy was dependent on genetic background (e.g., single nucleotide polymorphisms) and gender. Vitamin D demonstrated a complex relationship with biological aging, with deficiency linked to accelerated epigenetic age and supplementation showing potential to slow it. As antioxidants, vitamins C and E exhibited a biphasic, hormetic response; they mitigated oxidative damage at low doses but could act as pro-oxidants at high concentrations. Vitamins D and A were identified as crucial regulators of the immune system, modulating inflammatory responses and T-cell differentiation, while vitamins C and B12 were found to enhance cellular reprogramming and stem cell function, critical for tissue repair. However, results from large-scale RCTs were often mixed, with many studies showing no significant benefit of high-dose single-vitamin supplementation on all-cause mortality or major cardiovascular events, highlighting the importance of dosage, context, and combination with other nutrients.
  • Conclusion: Conclusion: Vitamins play a fundamental, multi-faceted role in promoting healthy aging by targeting the core biological hallmarks of aging. They function not merely as essential nutrients but as strategic modulators of epigenetics, oxidative stress, inflammation, and cellular repair. The evidence supports a hormetic model where appropriate, often moderate, dosing is key to unlocking their protective benefits, while supra-nutritional doses can be ineffective or even harmful. The future of vitamin-based anti-aging interventions lies in personalized nutrition strategies that consider an individual's genetic makeup, age, and specific health status. Moving forward, research must prioritize long-term, well-designed clinical trials that investigate combinations of vitamins and integrate functional outcomes to translate these potent biological mechanisms into effective strategies for extending human healthspan and longevity.
  • Keywords: Vitamin, Aging, Epigenetic, Oxidative stress, Longevity, Immune system