Background and Objectives: Stress can overload adaptive mechanisms, leading to epigenetic effects harmful to health. Research on the reversal of these effects is in its infancy. Early results suggest some meditation techniques have health benefits that grow with repeated practice. This study focused on possible transcriptomic effects of 38 years of twice-daily Transcendental Meditation^® (TM^®) practice. Materials and Methods: First, using Illumina^® BeadChip microarray technology, differences in global gene expression in peripheral blood mononuclear cells (PBMCs) were sought between healthy practitioners and tightly matched controls (n = 12, age 65). Second, these microarray results were verified on a subset of genes using quantitative polymerase chain reaction (qPCR) and were validated using qPCR in larger TM and control groups (n = 45, age 63). Bioinformatics investigation employed Ingenuity^® Pathway Analysis (IPA^®), DAVID, Genomatix, and R packages. Results: The 200 genes and loci found to meet strict criteria for differential expression in the microarray experiment showed contrasting patterns of expression that distinguished the two groups. Differential expression relating to immune function and energy efficiency were most apparent. In the TM group, relative to the control, all 49 genes associated with inflammation were downregulated, while genes associated with antiviral and antibody components of the defense response were upregulated. The largest expression differences were shown by six genes related to erythrocyte function that appeared to reflect a condition of lower energy efficiency in the control group. Results supporting these gene expression differences were obtained with qPCR-measured expression both in the well-matched microarray groups and in the larger, less well-matched groups. Conclusions: These findings are consistent with predictions based on results from earlier randomized trials of meditation and may provide evidence for stress-related molecular mechanisms underlying reductions in anxiety, post-traumatic stress disorder (PTSD), cardiovascular disease (CVD), and other chronic disorders and diseases.

Background: Our previous comparison of peripheral blood mononuclear cells (PBMCs) from long-term Transcendental Meditation^® (TM^®) practitioners and matched non-practitioner controls found 200 differentially expressed (DE) genes. Bioinformatics analyses of these DE genes suggested a reduced risk of diseases associated with stress and aging in the TM group. Here we assessed additional signs of reduced stress and aging. Methods: A sample of 15 of the 200 DE genes was studied using qPCR in PBMCs from 40-year TM practitioners (“Old TM”, n = 23) compared to a “Young Control” group (n = 19) and an “Old Control” group (n = 21) of non-meditators. In these three groups, plus a “Young TM”, 12-year practitioner group (n = 26), we also studied EEG-based parameters of cognitive function (the Brain Integration Scale (BIS), and latency of three components of the event-related potential (ERP)). Finally, using LC/MS/MS, we compared persistent levels of cortisol (F) and its inactive congener, cortisone (E), in hair. Results: qPCR analysis showed that 13 of the 15 genes were more highly expressed in Old Controls than in Young Controls. In the Old TM group, 7 of these 13 were lower than in Old Controls. Both TM groups had higher BIS scores than their age-matched controls. The Old TM group had shorter N2, P3a, and P3b latencies than the Old Control group, and latencies in the Old TM group were not longer than in the Young Control group. The Hair F/Hair E ratio was higher in the control subgroups than in their age-matched TM subgroups, and Hair F was higher in the Young Control and combined control groups than in the Young TM and combined TM groups. Conclusions: These results are consistent with reductions in biomarkers of chronic stress and biological age in long-term TM meditators. They are also consistent with results from the previous study suggesting that TM practice lowers energy consumption or leads to more efficient energy metabolism.