Betaine modulates age-related NF-κB by thiol-enhancing action

Depletion of glutathione levels and perturbations in redox status are considered to play a crucial role in aging and chronic inflammatory processes through the activation of redox sensitive transcription factors, including nuclear factor-kappa B (NF-kappa B). In the current study, we assessed the regulatory action of dietary betaine in the suppression of NF-kappa B by comparing kidney tissue from old, betaine-supplemented rats or non-betaine-supplemented rats (age 21 months) and 7 month-old rats. In addition, cultured HEK 293T cells were utilized for the molecular assessment of betaine's restorative ability of redox status when treating cells with potent glutathione (GSH)-depleting agents. Results showed that in old rats a short-term feeding (10 d) with betaine attenuated the age-related decrease in thiol levels, increase in reactive species and TNF alpha expression via NF-kappa B activation, compared to the young controls. These findings were verified in the cell-cultured system. Further investigations found that redox imbalance due to thiol depletion caused increased NF-kappa B activation, and cyclooxygenase (COX)-2 and TNFa levels, both of which were suppressed by betaine treatment. Based on both in vivo and in vitro data, we concluded that betaine exerts its efficacy by maintaining thiol status in the regulation of COX-2 and TNFa via NF-kappa B activation during aging.