Effects of long-term meditation on the expression of genes related to inflammation and their methylation status: A case-control study

Abstract

Background:Despite established benefits for mental and physical well-being, the precise underlying molecular mechanisms of the effects of meditation remain unclear. This study explored the hypothesis that long-term meditation practice downregulates the expression of genes associated with stress-induced inflammation. The expression of selected inflammation-related genes and their promoter methylation status were compared between long-term meditators and controls. Methods:Thirty experienced meditators and 30 age- and gender-matched non mediators participated in this case-control study. RNA and DNA were extracted from blood samples. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) with GAPDH normalization was used to measure the expression of eight inflammation-related genes (IFN-γ, IL-6, CCL-2, CCR-7, TNF-α, NF-κB, CXCL8, andCOX-2). Additionally, bisulfite-specific PCR and Sanger sequencing were performed to assess the methylation status of five of these genes (IL-6, TNF-α, IFN-γ, COX-2, and CXCL8) in their promoter regions. Results: The mean age of participants was 43.83 ± 9.92 years, and 63.34% in each group were male. Compared to controls, meditators showed significantly lower relative gene expression for IFN-γ (Fold change (FC)=7,p=0.045), IL-6 (FC=3.6,p=0.045), TNF-α (FC=2.73,p=0.038), NF-ƘB(FC=3.2,p=0.045), CXCL8 (FC=3.3,p=0.047), and COX-2 (FC=9.5,p=0.013). Furthermore, meditators exhibited significantly higher promoter region methylation in IL-6 (p < 0.001) and CXCL8 (p = 0.001). The methylation level at specific CpG sites showed that four out of 16 sites in IL-6 and five out of twelve sites in CXCL-8 gene had significantly higher methylation in meditators. Although no significant difference in the overall methylation level in the promoter regions of TNF-α and IFN-γ genes were detected, two out of 12 sites and one out of 27 sites in the TNF-α and IFN-γ genes, respectively, showed significantly higher methylation in meditators. Conclusion:These findings suggest that long-term meditation practice may contribute to reduced inflammation by downregulating the expression of specific inflammatory pathway genes and increasing their promoter methylation. Further research is needed to explore these potential mechanisms and their long-term health implications.