CELLULAR MARKERS OF YOGA

Presented by,

Mr. Thrinath M

Senior Research Fellow @ Y-SCAN Project

Research Scholar @ Human Genetics Dept. NIMHANS

Chaired by,

Dr. Monojit Debnath

Additional Professor,

Dept. of Human Genetics, NIMHANS

CONTENTS

1. Introduction

2. Evidences indicating the impact of yoga therapy at Cellular and

Molecular level

3. Evidences indicating the impact of yoga therapy at Genetic and

Epigenetic level

4. Conclusion

5. References

Benefits of Yoga Practice

Improved Brain

Function Lower Stress Levels

Increased Flexibility

Lower Blood

Pressure

Improved Immune Function

Reduced Chronic Neck &

Back Pain

Lower Blood Sugar

Levels in Diabetes

Improved Sense of Balance

Stronger Bones

Healthy Weight

Lower Risk of Hearth Diseases

• Yoga is one of the most common integrative

medicine (IM) modalities and related

practices.

• Accumulating evidences shown that yoga

improves wellness in healthy people and have

benefits for patients.

• However, the mechanisms of action of yoga

on the mind-body system are largely

unknown.

INTRODUCTION

EVIDENCES INDICATING THE EFFECT OF YOGA THERAPY AT MOLECULAR & CELLULAR LEVEL

EFFECT OF YOGA ON OXIDATIVE STRESS

ROS:

Superoxide anion (O2-)

Hydrogen peroxide (H2O2)

Hydroxyl Radicals (OH_

)

Anti-oxidants:

Glutathione, Melatonin, Ascorbic acid

or vitamin C, …

Enzymes: SOD, Catalase, Glutathione

systems…

OXIDATIVE STRESS

Oxidative stress, defined as a disturbance in the

balance between the production of reactive oxygen

species (free radicals) and antioxidant system, which

is in charge of keeping the homeostasis of the

organism (Betteridge, 2000)

Internal sources of free radicals: Mitochondria, Peroxisomes, Inflammation, Phagocytosis..

External sources of free radicals: Cigarette smoke, Environmental pollutants, Radiation… (V. Lobo

et al., 2010)

MARKERS OF OXIDATIVE AND ANTI-OXIDATIVE STATUS

• Oxidative stress:

• DNA/RNA damage: 8-hydroxy-2’-deoxy guanosine (8-OHdG)

• Lipid peroxidation: Malondialdehyde (MDA)

• Protein oxidation / nitration: carbonylation or protein nitration (3-

nitrotyrosines)

• Total antioxidant status (TAOS)

• Glutathione (GSH) and oxidised glutathione

• antioxidant enzymes: Superoxide dismutase, Catalase.. Trolox equivalent

antioxidant capacity assay (TEAC)

• Oxygen radical antioxidant capacity (ORAC) assay

OS

Sperm DNA/mt

damage

Meditation and yoga based life style

OS and ODD and improvement in sperm

DNA integrity

• seminal mean ROS levels (p<0.05), sperm DFI

(p<0.001), 8-OHdG (p<0.01) levels in fathers of children

with RB

• Shorter relative mean telomere length in the sperm

(Rima Dada et al., 2016)

• Regularly yoga practitioners had lower systemic oxidative stress (high TAOS

and low MDA and homocysteine) compared to those who have a relatively

sedentary lifestyle despite lack of any medical disorders. (Bandi Hari

Krishna et al., 2015)

OS

Sperm DNA/mt

damagemtDNA

damageInflammation

Genetic

instability

Increased

Aging

Yoga Therapy

Improved

sperm quality

Decreased

inflammation

levels

Genetic

integrityYouthfulnessStable

mitochondria

Cellular

damage

Increased

cell longevity

EFFECT OF YOGA ON OXIDATIVE STRESS

EFFECT OF YOGA THERAPY ON CANCER

CANCER

• Cancer is a group of diseases involving abnormal cell

growth with the potential to invade or spread to other

parts of the body.

• There are more than 100 types of cancer:

• breast cancer,

• skin cancer,

• lung cancer,

• colon cancer,

• prostate cancer,

• lymphoma. ...

• Cancer stem cells (CSCs) are stem-like tumor cells that contribute towards tumor

growth, maintenance and recurrence

CANCER STEM CELLS (CSCS)

CSCs

Mature

cancer cells

CSCs

Mature

cancer cells

• Yoga therapy has the potential to modulate CSCs micro-

environment by following mechanisms:

• Reducing HIF-1 (Hypoxia Induced factor-1) activity by

enhanced oxygenation

• Increased NK cell (CD56+ cells) activity thereby enhanced

CSC lysis (Masatada Wachi et al., 2007)

• By minimizing the aberrant expressions or activities of

various hormones, cytokines, chemokines and tumor

signaling pathways.

• Yoga therapy may have a synergistic effect with

conventional treatment in preventing cancer progression

and recurrences (Bhargav.H et al., J Stem Cells. 2012)

YOGA THERAPY AND TISSUE HOMEOSTASIS

MESENCHYMAL STEM CELLS (MSCS)

• MSCs (CD90, CD105 and CD73) are non-

hematopoietic stromal cells present in the bone

marrow and connective tissues.

• Capable of differentiating into mesenchymal

tissue: Bone, cartilage, adipose tissue and

muscle

• Play an important role in tissue homeostasis.

YOGA THERAPY AND MESENCHYMAL STEM CELLS (MSCS) TRAFFICKING

• After three weeks Intensive MBT retreat, 90 %

(n=108) of participants had increased levels of

peripheral blood stem cells (Rao KS et al.,

2015).

(Nitya Shree et al., 2016).

IMPACT OF YOGA THERAPY ON GENE EXPRESSION

GENE EXPRESSION

• Gene expression is the process by which information

from a gene is used in the synthesis of a functional gene

product.

• Gene expression is influenced by external and internal

factors.

• External factors: hormones, cytokines, etc.

• Internal factors: Metabolism, growth, etc.

EFFECT OF YOGA THERAPY ON GENE EXPRESSION

• Rapid changes in global gene expression profiles in the

peripheral blood mononuclear cells (PBMCs) were assessed.

• Qu et al. (2013) investigated the global gene expression in

PBMCs (>47,000 transcripts) in healthy people who practiced

either a comprehensive yoga program (SK&P) or a control

regimen (nature walk and listening to a relaxing music) (N = 10)

• Figure (C) is Venn diagram

indicating the overlap in the

genes commonly regulated by

the yoga and control regimens

Heatmaps of the differentially

expressed genes induced by the yoga

(A) and control (B) regimens.

(Qu S et al., 2013)

• Yoga therapy down regulates NF-kB and IRF-1

transcription factors

• Decreases apoptotic gene expression

• Balancing the levels of various pro-inflammatory

pathway genes (IL-6) and anti-inflammatory

genes (IL-10)

Change in CD4 cell counts between pre and post

yoga interventionChange in viral load between pre and post yoga

intervention

A piolet study on HIV+ patients, yoga therapy lead to increases in CD4/CD8 ration and

decrease in viral load (n=18) (BP Hari Chandra et al., 2019)

EFFECT OF YOGA THERAPY ON IMMUNE CELL COUNT

IMPACT OF YOGA THERAPY AT GENOMIC AND EPIGENOMIC LEVEL

• The Nobel Prize in Physiology or Medicine 2009

• Elizabeth H. Blackburn

• Carol W. Greider

• Jack W. Szostak

• “how chromosomes are protected by telomeres and

the enzyme telomerase“

• An important piece in the puzzle – human ageing, cancer,

and stem cells

EFFECT OF YOGA THERAPY ON TELOMERE & TELOMERASE

• Telomeres, the repetitive sequences that protect the ends of chromosomes.

• Telomeres progressively shorten throughout life.

• Shorter telomere length associated with lifestyle disorders.

• Telomerase is an enzyme which maintains the telomere length.

• A three week intense MBT retreat with healthy individuals (n=108), showed 45% one

fold increased and 27% with 2 fold increase in telomerase activity may lead to

increased longevity and better quality of life. (Rao KS et al., 2015)

• Two years yoga practice (Yoga group, n=15) and age, gender and body mass index

matched sedentary healthy general population (Control group, n=18) showed shorter

lymphocyte telomere length (LTL) in control group than in yoga group (p<0.001)

MECHANISM OF TELOMERE LENGTH PROTECTION THROUGH YOGA

(Mrithunjay et al., 2018)

OS

Sperm DNA/mt

damageGenetic

instability

Increased

Aging

Yoga Therapy

Increased

male fertilityGenetic

integrityYouthfulness

Impact of Yoga therapy on some of

the aspect at Genomic Level

EPIGENETICS

“epi-“ means above in Greek.

DNA modifications that do not change the DNA

sequence can affect gene activity.

Chemical compounds that are added to single

genes can regulate their activity; these

modifications are known as epigenetic changes.

• A cross-sectional pilot study used a subsample (n = 28) from a RCT investigating the impact of an

8-week yoga intervention in a community population of women reporting psychological distress

(N = 116)

• Measured for interleukin-6 (IL-6), tumor necrosis factor (TNF) and C-reactive protein (CRP)

protein levels, and DNA methylation of these genes and the global indicator, LINE-1.

• Reduced methylation of the TNF region in the yoga group relative to the waitlist control

(p=0.025)

• This study reports a robust association between engagement with an 8-week yoga intervention

and reduction in mean methylation of TNF (5.5%)

IMPACT OF YOGA AT EPIGENETIC LEVEL

CONCLUSION

• Data suggest possible roles of yoga practice and related practices can decrease

systemic oxidative stress which may assist to prevent and/or alleviate deterioration of

related diseases.

• Gene expression data suggests that previously reported effects of yoga practices

have an integral physiological component at the molecular level which is initiated

immediately during practice and may form the basis for the long term stable effects.

REFERENCES

• Free radicals, antioxidants and functional foods: Impact on human health. V. Lobo et al., Pharmacogn Rev. 2010

Jul-Dec; 4(8): 118–126.

• Effect of Yoga on Immune Parameters, Cognitive Functions, and Quality of Life among HIV-Positive

Children/Adolescents: A Pilot Study BP Hari Chandra

• Antiaging Effects of an Intensive Mind and Body Therapeutic Program through Enhancement of Telomerase

Activity and Adult Stem Cell Counts. Rao KS et al. J Stem Cells. 2015;10(2):107-25.

• Implication of Asana, Pranayama and Meditation on Telomere Stability. Mrithunjay et al., IJOY, 2018

• Association of Leukocyte Telomere Length with Oxidative Stress in Yoga Practitioners. Bandi Hari Krishna et al.,

Journal of Clinical and Diagnostic Research. 2015 Mar,Vol-9(3).

• Rapid Gene Expression Changes in Peripheral Blood Lymphocytes upon Practice of a Comprehensive Yoga

Program.Qu S, Olafsrud SM, Meza-Zepeda LA, Saatcioglu F (2013) PLOS ONE 8(4): e61910.

• Effect of Yoga on Immune Parameters, Cognitive Functions, and Quality of Life among HIV-Positive

Children/Adolescents: A Pilot Study. BP Hari Chandra et al.,, Int J Yoga. 2019 May-Aug; 12(2): 132–138.

•

• Effects of yoga on natural killer cell counts in early breast cancer patients undergoing conventional treatment.

Masatada Wachi, et al., Med Sci Monit, 2007; 13(2): CR57-70

• Enhancement of cancer stem cell susceptibility to conventional treatments through complementary yoga therapy:

possible cellular and molecular mechanisms. Bhargav.H et al., J Stem Cells. 2012.

• Can yoga therapy stimulate stem cell trafficking from bone marrow? Nitya Shree et al., Journal of Ayurveda and Integrative

Medicine 7 (2016).