Nrf2 cell signaling pathway is responsible for the antioxidant effect of resveratrol in aging

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Introduction One of the markers of aging is oxidative stress, a condition characterized by an increase in free radicals concomitant with a reduction in antioxidant defenses. Within this, resveratrol is a compound that has been shown to act as a potent antioxidant. However, few studies highlight the cellular signaling pathways that are activated or inhibited during aging and that are responsible for this biological effect. Aim To verify the antioxidant profile of resveratrol (5 μM) in leukocytes from donors in different age groups. Methods The project was approved by the Ethics Committee. Individuals were divided into three groups: 20–39, 40–59, and 60–80 years old. After separating the leukocytes, assays were performed to evaluate the AMPK (AMP‐activated protein kinase) and Nrf2 (erythroid nuclear factor 2‐related factor 2) pathways. In addition, luciferase assay and enzyme‐linked immunosorbent assay were performed to evaluate transcription factor activation and Nrf2 expression, respectively. The analysis between age and treatment was performed using Pearson correlation (* P < 0.05). Results There was a reduction in the antioxidant effect of resveratrol during the aging process. In leukocytes from donors over 60 years of age, the AMPK pathway was silenced. Nrf2 was active at all ages. There was an increase in the activation of the transcription factor and phosphorylated protein in all age groups. Conclusions Nrf2 is an important biochemical mechanism responsible for the antioxidant effect of resveratrol. This effect diminishes with aging but is still observed. Geriatr Gerontol Int 2024; 24: 954–961 .