Share This Article:

An Intensive Mind and Body Therapeutic Program Leads to Alteration in Gene Expression Critical to Aging Process in Peripheral Blood Stem Cells

Full-Text HTML Download Download as PDF (Size:300KB) PP. 89-95
DOI: 10.4236/aar.2015.43011    3,250 Downloads   3,696 Views  


Objective: Waiting to look young is not a new idea; the search for effective treatments prolonging youthfulness has been going on over many decades. Many scientific evidences have been suggestive of intensive or prolonged mind and body therapies (MBT) improving overall wellness and have anti-aging effects. However, the genetic basis of MBT-induced anti-aging and youthfulness are largely unknown. It is also known that aging adversely affects hematopoiesis in human through controlling compromised hematopoietic stem cells (HSC) and peripheral blood mononuclear cells (PBMNC’s). In this paper, we focus on evaluating changes in the expression levels of a critical panel of genes that regulates aging in PBMNC’s isolated from participants from MBT program. Design: Here, we have investigated the effects of a short intensive MBT program on aging related gene expression changes in the peripheral blood stem cells using affymetrix DNA microarray platform. A total of 108 people selected form many ethnicities were enrolled in the study; 38 men and 70 women (aged 18 - 90) randomly assigned for the study. PBMNC’s were collected from the volunteers before and after the completion of the MBT program and evaluated for meditation by examining gene expression patterns in peripheral blood stem cells. Results: Critical pathways known to regulate aging process such as pro-inflammatory TNF alpha/NF-kB, IL-12 signaling pathway, hypoxic HIF-1-alpha, key regulator of programmed cell death, C-MYC, and P38 MAPK (mitogen-activated protein kinase) signaling pathway found to be dysregulated in the cohorts compared to subjects prior to MBT program. Furthermore, GATA-2 and Bmi1, key regulators of hemtopoiesis and adult stem cells numbers, went up in the mediated group. Additionally, key pro-inflammatory mediators IFN? and STAT-2 went down in the mediated group. Conclusion: MBT augments critical genes in PMBC which upregulate hematopoiesis and stem cell numbers and also controls genes that regulate age-related complications.

Cite this paper

Rao, K. , Chakrabarti, S. , Dongare, V. , Sharath, B. , Vikas, H. , Chetana, K. and Deb, K. (2015) An Intensive Mind and Body Therapeutic Program Leads to Alteration in Gene Expression Critical to Aging Process in Peripheral Blood Stem Cells. Advances in Aging Research, 4, 89-95. doi: 10.4236/aar.2015.43011.


[1] The Academy of Medical Sciences (2009) Rejuvenating Aging Research: A Report by the Academy of Medical Sciences. The Academy of Medical Sciences, London.
[2] Gems, D. and Partridge, L. (2013) Genetics of Longevity in Model Organisms: Debates and Paradigm Shifts. Annual Review of Physiology, 75, 621-644.
[3] Kirkwood, T.B. (2005) Understanding the Odd Science of Aging. Cell, 120, 437-447.
[4] Vijg, J. and Campisi, J.P. (2008) Puzzles, Promises and a Cure for Ageing. Nature, 454, 1065-1071.
[5] Monti, D.A., Sufian, M. and Peterson, C. (2008) Potential Role of Mind-Body Therapies in Cancer Survivorship. Cancer, 112, 2607-2616.
[6] Hartmut, G. and Zheng, Y. (2013) Cdc42 and Aging of Hematopoietic Stem Cells. Current Opinion in Hematology, 20, 295-300.
[7] Gene Ontology Consortium. (2004) The Gene Ontology (GO) Database and Informatics Resource. Nucleic Acids Research, 32, D258-D261.
[8] Stokoe, D., Campbell, D.G., Nakielny, S., Hidaka, H., Leevers, S.J., Marshall, C. and Cohen, P. (1992) MAPKAP Kinase-2; A Novel Protein Kinase Activated by Mitogen-Activated Protein Kinase. The EMBO Journal, 11, 3985-3994.
[9] Tamura, K., Sudo, T., Senftleben, U., Agnes M Dadak, A.M., Johnson, R. and Karin, M. (2000) Requirement for p38alpha in Erythropoietin Expression: A Role for Stress Kinases in Erythropoiesis. Cell, 102, 221-231.
[10] del Barco Barrantes, I., Coya, J.M., Maina, F., Arthur, J.S. and Nebreda, A.R. (2011) Genetic Analysis of Specific and Redundant Roles for p38alpha and p38beta MAPKs during Mouse Development. Proceedings of the National Academy of Sciences of the United States of America, 108, 12764-12769.
[11] Ono, K. and Han, J. (2000) The p38 Signal Transduction Pathway: Activation and Function. Cellular Signalling, 12, 1- 13.
[12] Menssen, A. and Hermeking, H. (2002) Characterization of the c-MYC-Regulated Transcriptome by SAGE: Identification and Analysis of c-MYC Target Genes. Proceedings of the National Academy of Sciences of the United States of America, 99, 6274-6279.
[13] Koch, S. and Claesson-Welsh, L. (2012) Signal Transduction by Vascular Endothelial Growth Factor Receptors. Cold Spring Harbor Perspectives in Medicine, 2, a006502.
[14] Gilmore, T.D. and Wolenski, F.S. (2012) NF-κB: Where Did It Come from and Why? Immunological Reviews, 246, 14-35.
[15] Gupta, S., Bi, R., Kim, C., Chiplunkar, S., Yel, L. and Gollapudi, S. (2005) Role of NF-κB Signaling Pathway in Increased Tumor Necrosis Factor-α-Induced Apoptosis of Lymphocytes in Aged Humans. Cell Death & Differentiation, 12, 177-183.
[16] Derynck, R. and Feng, X.H. (1997) TGF-β Receptor Signaling. Biochimica et Biophysica Acta, 24, F105-F150.
[17] Rezvani, H.R., Ali, N., Serrano-Sanchez, M., Dubus, P., Varon, C., Ged, C., et al. (2011) Loss of Epidermal Hypoxia-Inducible Factor-1α Accelerates Epidermal Aging and Affects Re-Epithelialization in Human and Mouse. Journal of Cell Science, 124, 4172-4183.
[18] Cho, Y.S., Bae, J.M., Chun, Y.S., Chung, J.H., Jeon, Y.K., Kim, I.S., et al. (2008) HIF-1α Controls Keratinocyte Proliferation by Up-Regulating p21 (WAF1/Cip1). Biochimica et Biophysica Acta, 1783, 323-333.
[19] Rezvani, H.R., Ali, N., Nissen, L.J., Harfouche, G., de Verneuil, H., Taieb, A., et al. (2011) HIF-1α in Epidermis: Oxygen Sensing, Cutaneous Angiogenesis, Cancer, and Non-Cancer Disorders. Journal of Investigative Dermatology, 31, 1793-1805.
[20] Yu, L., Wang, L.T. and Chen, S.W. (2010) Endogenous Toll-Like Receptor Ligands and Their Biological Significance. Journal of Cellular and Molecular Medicine, 14, 2592-2603.
[21] Hussain, S., Wilson, J.B., Medhurst, A.L., Hejna, J., Witt, E., Ananth, S., et al. (2004) Direct Interaction of FANCD2 with BRCA2 in DNA Damage Response Pathways. Human Molecular Genetics, 12, 1241-1248.
[22] Lacy, D.B. and Collier, R.J. (2002) Structure and Function of Anthrax Toxin. Current Topics in Microbiology and Immunology, 271, 61-85.
[23] Prendergast, G.C. (1999) Mechanisms of Apoptosis by c-Myc. Oncogene, 18, 2967-2987.
[24] Mishina, Y. (2003) Function of Bone Morphogenetic Protein Signaling during Mouse Development. Frontiers in Bioscience, 8, d855-d869.
[25] Matsumoto, T., Sakari, M., Okada, M., Yokoyama, A., Takahashi, S., Kouzmenko, A., et al. (2013) The Androgen Receptor in Health and Disease. Annual Review of Physiology, 75, 201-224.
[26] Falkenstein, E., Tillmann, H.-C., Christ, M., Feuring, M. and Wehling, M. (2000) Multiple Actions of Steroid Hormones—A Focus on Rapid, Nongenomic Ef-fects. Pharmacological Reviews, 52, 513-555.
[27] Salameh, A., Galvagni, F., Anselmi, F., De Clemente, C., Orlandini, M. and Oliviero, S. (2010) Growth Factor Stimulation Induces Cell Survival by c-Jun. ATF2-Dependent Activation of Bcl-XL. Journal of Biological Chemistry, 285, 23096-23104.
[28] Guo, Z.Y., Dai, B.J., Jiang, T.Y., Xu, K.X., Xie, Y.Q., Kim, O., et al. (2006) Regulation of Androgen Receptor Activity by Tyrosine Phosphorylation. Cancer Cell, 10, 309-319.
[29] Kimita, S., Irina, S. and Mitchell, G.A. (2002) Signaling Pathway Leading to Metastasis Is Controlled by N-Cadherin and the FGF Receptor. Cancer Cell, 2, 301-314.
[30] Pflanz, S., Timans, J.C., Cheung, J., Rosales, R., Kanzler, H., Gilbert, J., et al. (2002) IL-27, a Heterodimeric Cytokine Composed of EBI3 and p28 Protein, Induces Proliferation of Naive CD4+ T Cells. Immunity, 16, 779-790.
[31] Burton, J.D., Bamford, R.N., Peters, C., Grant, A.J., Kurys, G., Goldman, C.K., et al. (1994) A Lymphokine, Provisionally Designated Interleukin T and Produced by a Human Adult T-Cell Leukemia Line, Stimulates T-Cell Proliferation and the Induction of Lymphokine-Activated Killer Cells. Proceedings of the National Academy of Sciences of the United States of America, 91, 4935-4939.
[32] Trinchieri, G. (1995) Interleukin-12: A Proinflammatory Cytokine with Immunoregulatory Functions That Bridge Innate Resistance and Antigen-Specific Adaptive Immunity. Annual Review of Immunology, 13, 251-276.
[33] Duncan, M.R., Frazier, K.S., Abramson, S., Williams, S., Klapper, H., Huang, X., et al. (1999) Connective Tissue Growth Factor Mediates Transforming Growth Factor β-Induced Collagen Synthesis: Down-Regulation by cAMP. FASEB Journal, 13, 1774-1786.
[34] Reich, N.C. (2013) STATs Get Their Move on. JAK-STAT, 2, e27080.
[35] Jurk, D., Wilson, C. and Passos, J.F. (2014) Chronic Inflammation Induces Telomere Dysfunction and Accelerates Ageing in Mice. Nature Communications, 2, 4172.
[36] Jun, H., Chantal, D., Masahide, O. and Mercola, D. (2003) The Activation of c-Jun NH2-Terminal Kinase (JNK) by DNA-Damaging Agents Serves to Promote Drug Resistance via Activating Transcription Factor 2 (ATF2)-Dependent Enhanced DNA Repair. Journal of Biological Chemistry, 278, 20582-20592.
[37] Liang, H.Y., Masaro, E.J., Nelson, J.F., Strong, R., McMahan, C.A. and Richardson, A. (2003) Genetic Mouse Models of Extended Lifespan. Experimental Gerontology, 38, 1353-1364.
[38] Shackelford, R.E. (2005) Pharmacologic Manipulation of the Ataxia-Telangiectasia Mutated Gene Product as an Intervention in Age-Related Disease. Medical Hypotheses, 65, 363-369.
[39] Rodrigues, N.P., Janzen, V., Forkert, R., Dombkowski, D.M., Boyd, A.S., Orkin, S.H., et al. (2005) Haploinsufficiency of GATA-2 Perturbs Adult Hematopoietic Stem Cell Homeostatis. Blood, 106, 477-484.
[40] Park, I.-K., Morrison, S.J., and Clarke, F.M. (2004) Bmi1, Stem Cells, and Senescence Regulation. Journal of Clinical Investigation, 113, 175-179.
[41] Syntichaki, P., Troulinaki, K. and Tavernarakii, N. (2007) eIF4E Function in Somatic Cells Modulates Ageing in Caenorhabditis elegans. Nature, 445, 922-926.
[42] Chen, X.F., Overcash, R., Green, T., Hoffman, D., Asch, A.S. and Ruiz-Echevarría, M.J. (2011) The Tumor Suppressor Activity of the Transmembrane Protein with Epidermal Growth Factor and Two Follistatin Motifs 2 (TMEFF2) Correlates with Its Ability to Modulate Sarcosine Levels. Journal of Biological Chemistry, 18, 16091-16100.
[43] Mooijaart, S.P., van Heemst, D., Noordam, R., Rozing, M.P., Wijsman, C.A., de Craen, A.J., et al. (2011) Polymorphisms Associated with Type 2 Diabetes in Familial Longevity: The Leiden Longevity Study. Aging, 3, 55-62.

comments powered by Disqus

Copyright © 2017 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.