Transcriptomics of Long-Term Meditation Practice: Evidence for Prevention or Reversal of Stress Effects Harmful to Health Author: Supaya Wenuganen1, Kenneth G Walton1,2, Shilpa Katta3,4, Clifton L Dalgard4, Gauthaman Sukumar4, Joshua Starr4, Frederick T Travis5, Robert Keith Wallace1, Paul Morehead1, Nancy K Lonsdorf1, Meera Srivastava4, John Fagan1,6 Affiliation: <sup>1</sup> Department of Physiology and Health, Maharishi International University, Fairfield, IA 52556, USA. <sup>2</sup> Institute for Prevention Research, Fairfield, IA 52556, USA. <sup>3</sup> Cancer Genomics Research Laboratory (CGR), Division of Cancer Epidemiology and Genetics, NCI Leidos Biomedical Research, Inc., Gaithersburg, MD 20877, USA. <sup>4</sup> Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. <sup>5</sup> Center for Brain, Cognition, and Consciousness, Maharishi International University, Fairfield, IA 52557, USA. <sup>6</sup> Health Research Institute, Fairfield, IA 52556, USA. Conference/Journal: Medicina (Kaunas) Date published: 2021 Mar 1 Other: Volume ID: 57 , Issue ID: 3 , Pages: 218 , Special Notes: doi: 10.3390/medicina57030218. , Word Count: 308 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. Keywords: allostatic load; biological aging; chronic stress; energy metabolism; epigenetic effects; gene expression; transcendental meditation. PMID: 33804348 PMCID: PMC8001870 DOI: 10.3390/medicina57030218