Silencing of the Nrf2 pathway in aging promotes a decrease in the anti-inflammatory effect of resveratrol.
Filipe Nogueira Franco1, Brenda Evangelista Peixoto1, Glaucy Rodrigues de Araújo1
1Biochemistry Laboratory of Aging and Correlated Diseases, Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Av. Antônio Carlos 6627, 30161-970, Belo Horizonte MG Brazil.
Resveratrol reduces inflammation and oxidative stress markers like TNF and IL-6 in aging cells, particularly via the Nrf2 pathway. This polyphenol shows promise in combating age-related diseases by modulating these key inflammatory responses.
Area of Science:
- Gerontology
- Immunology
- Molecular Biology
Background:
- Aging is characterized by increased oxidative stress and chronic low-grade inflammation, termed "inflammaging."
- Inflammaging contributes to age-related diseases.
- Resveratrol, a polyphenol, possesses known antioxidant and anti-inflammatory properties.
- The transcription factor Nrf2 regulates cellular defense against oxidative stress.
Purpose of the Study:
- To investigate the effect of resveratrol on cytokine production in leukocytes from different age groups.
- To evaluate the role of the Nrf2 pathway in resveratrol's anti-inflammatory effects.
- To assess how age influences resveratrol's impact on oxidative stress and inflammation.
Main Methods:
- Leukocytes were isolated from three age groups (20-39, 40-59, 60-80 years).
- Cells were treated with resveratrol (5µm) and/or peroxide (150 µM) for 24 hours, with and without the Nrf2 inhibitor ML385.
- Cytokine levels (TNF, IL-6, IL-10) were measured using ELISA.
Main Results:
- Peroxide stimulation increased TNF and IL-6 levels in all age groups.
- Resveratrol decreased TNF and IL-6 levels, both at basal and peroxide-induced conditions.
- Resveratrol enhanced IL-10 production primarily in the youngest age group.
- These effects were observed irrespective of Nrf2 pathway inhibition by ML385.
Conclusions:
- Resveratrol demonstrates significant antioxidant and anti-inflammatory effects relevant to aging.
- The Nrf2 pathway is implicated in resveratrol's ability to mitigate oxidative stress and inflammation.
- Resveratrol may be a valuable therapeutic agent for preventing age-related inflammatory conditions, with potentially age-dependent efficacy.
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