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Finding the OM in GenOMics

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A recent climb in the number of people taking up a regular yoga or meditation practise has seen the terms “downward dog” and “tree pose” enter the everyday vocabulary of many. But what scientific evidence exists that supports the benefits of a regular yoga and meditation practise?

Birth of the yogi


A multidimensional practise, yoga entwines breathing practises, meditation and movement to unite the body and mind. It is classed as a mind-body intervention (MBI), an umbrella term that encompasses hypnosis, meditation, tai chi and visual imagery, in addition to yoga.

The word “yoga” comes from a Sanskrit root “yuj” which means “union”, or “yoke”, “to join”, “to direct and concentrate one's attention”, with the roots of yoga being grounded firmly in the eastern world. Archaeological explorations undertaken in the early 20th century uncovered male statues seated in the historic “lotus” position. The figures date back to the Indus Valley Civilization that occupied what is now a modern-day Pakistan and parts of India, and thus yoga is estimated to be over 5000 years old.

Over time, a multitude of forms of yoga have evolved, including Kundalini, Anusara, Ashtanga, Vanyasa to Bikram yoga. Whilst the popularity of yoga grows, in parallel, the different styles of yoga emerging also grow. In modern day America, 36 million people are estimated to practise yoga and meditation regularly, prompting the nickname “yogi” to define an individual that adopts a yoga practise.1 How can it be that a spiritual practise from the eastern world has migrated globally with such popularity? Yoga and meditation are not simply hobbies that you choose to dip in and out of as you please; to make spiritual “progress” one must make a commitment. So why do people commit to yoga?

The increasing popularity of yoga and meditation has spawned surplus scientific research that explores the myriad of self-reported benefits “yogis” claim to experience. But are these benefits supported by robust scientific evidence? What cellular and molecular mechanisms underpin them? In recent years, the developments in scientific technology has produced exciting research that brings scientists ever closer to unravelling the mystery of the mind-body connection.

Yoga and genetics


Thanks to the field of epigenetics, we now know that our genes are not simply “fixed” at birth, they can in fact be modified by our environment and lifestyle choices. To understand the molecular and cellular underpinnings of yoga’s self-reported benefits, there is no better place to start than at the core of our being – our genetics; and particularly, how yoga and meditation may alter our gene expression.

“By looking at changes in gene expression, we can understand how mind-body interventions get under the skin and improve our health and well-being. Besides uncovering the underlying mechanism, gene expression can also be used as an objective measure to track improvements in health as one begins to practice mind-body techniques, rather than relying solely on self-report measures that are common in psychology”, says Ivana Burić, PhD, a researcher in the field of MBI’s at Radboud University.

What evidence currently exists, and what challenges do scientists in this field of study face?

Yoga and inflammation


Increased expression of inflammatory molecules such as cytokines (including the interleukins (IL’s) and tumor necrosis factors (TNFs)) are major markers of chronic stress and ill-health.2 As such, the literature in the field is largely dominated by research studies exploring the impact of yoga and meditation on inflammatory processes.

A longitudinal, randomized controlled study explored the impact of a 3-month Iyengar yoga program, a form of Hatha yoga, on inflammatory processes in breast cancer survivors suffering from fatigue.3 The women were randomized to either the yoga intervention group (16 participants), or a 12-week health education control condition (15 participants). 

Genome-wide transcriptional profiling highlighted a total of 153 downregulated genes typically involved in anti-viral responses across the yoga group compared to controls after completion of the program. The researchers declared a 15% gene expression change as statically significant, unlike other experiments that have declared 20% as significant.

Furthermore, using Transcription Element Listening Systems (TELiS), the researchers demonstrated that the yoga group participants had reduced transcription activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB), a protein complex that plays a critical role in the immune response by regulating cytokine production. Similarly, reduced activity of cAMP response element-binding (CREB) transcription factors was highlighted in the yoga group. The researchers noted that this may imply reduced sympathetic nervous system signalling through β-adrenergic receptors, which typically activates NF-KB and upregulates pro-inflammatory cytokine genes.

Combined, these findings suggest a substantial down regulation of inflammatory processes as a result of adopting a regular yoga practise. Nonetheless – the study is not without its flaws. The authors note that the yoga conditions were not matched for class frequency or duration, and thus it is possible that the benefits observed in the yoga group are a result of the higher number of intervention hours received when compared to controls.

Yogic meditation and inflammation


The effects of yogic meditation on inflammatory processes have also been explored in a variety of populations. One study looked particularly at an interesting pool of participants: 39 dementia caregivers, a subset of the population that have previously shown to possess heightened levels of inflammatory biomarkers.4 Participants were randomized to either a program of Kirtan Kriya Meditation (KKM), a 12-minute yogic meditation chanting practise that is undertaken at the same time daily, established by the Kundalini yoga teacher Yogi Bhajan, or Relaxing Music (RM) for 12 minutes per day, for a total of 8 weeks. Genome-wide transcriptional profiles were obtained from a blood serum sample that was analyzed at baseline and at 8-weeks post follow up.

Results illustrated decreased NF-KB expression after 8-weeks of yogic meditation, and an increase in antiviral gene expression. Whilst the authors recognize the parallels between these findings and those of previous randomized controlled experiments, they too acknowledge limitations that may impact the credibility of the data. The sample size was small; hence a relatively low number of up-regulated and down-regulated genes were found to be statistically significant. 

Yoga in “non-clinical” populations


A comprehensive review published in Frontiers in Immunology by Burić and colleagues discusses eighteen studies that investigate gene expression changes induced by meditation and related practises.5 It becomes apparent, when focusing specifically on yoga research, that a major limitation in the field is the use of solely “clinical” samples diagnosed with a medical condition. Of course, this is not representative of the general population that practise yoga globally.

In their pilot study published in Nature, Harkess et al  regard themselves as one of the first teams to explore yoga and immunological markers in a non-clinical population whilst also analysing DNA methylation.6 DNA methylation is a common epigenetic mechanism that involves the addition of a methyl group to the cytosine ring in the DNA structure, ultimately silencing the gene encoded by the DNA.

The scientists investigated the molecular impact of an 8-week yoga program on a sample of 28 women experiencing chronic stress. The yoga program consisted of one hour’s yoga practise on average per week. Blood serum samples were obtained to compare DNA methylation patterns in women that completed the yoga intervention to a control group that had not.

Their results were surprising. Indeed the 8-week yoga program was associated with changes in immune protein expression and DNA methylation biomarkers, however, the changes were dissimilar to those observed in previous research.

The yoga group demonstrated a 5.5% reduction in DNA methylation of the tumor necrosis factor (TNF), a pro-inflammatory cytokine that is secreted by inflammatory cells, when compared to the control group, in addition to increased IL-6 levels. These results were not found to be statistically significant, again attributed to the use of a small sample size. A 2018 review published in the Journal of Clinical Epigenetics by Mody notes that this remains an unfortunate common theme in MBI research.7 

The possibility that Harkess et al.’s findings are an anomaly cannot be excluded. However, they pose new questions and warrant further extensive research into the molecular impact of yoga on markers of the immune system in larger, “non-clinical” populations.

The field is “stretched” 


A beautiful trait of yoga is that the practise is unique to the individual. Duration, frequency and style of practise are subjective and may change over time. From a research perspective, this is problematic. It proves challenging to standardize and control experiments. Resources are stretched in terms of conducting longitudinal research and heterogeneity exists across the literature at this time point.

“The thing is that genes can change expression in the response to many different things in our social or physical environment, but we are only beginning to understand what affects gene expression and how quickly it happens. It is very important to measure and control for as much as we can of the things that can change during the course of research intervention. For instance, some study participants could choose to eat healthier or exercise more during their participation in an 8—week meditation or yoga research intervention, which could then be attributed to meditation or yoga if it is not accounted for in the analysis”, says Burić.

Burić and team’s review calls for large-scale studies with standardized interventions that allow for comparison across studies to surmount these issues.

Whilst the cellular and molecular mechanisms contributing to the “feel good” factor of MBI’s remain elusive, Burić suggests that evidence thus far does not define any major differences between different types of mindful movement in terms of their impact on wellbeing. For yogis and meditators alike, this is good news, as “it means that no matter what technique you choose to integrate into your daily life, it will show improvements as long as you are consistent in your practice.  So, if you don’t like yoga, maybe try tai chi or mindful movement instead.”

As Mody puts eloquently, “If evolution is to be believed, certainly the growing practice of mind-body-interventions like yoga, and their growing popularity, will one day have their say in our genomic makeup”. 

References: 
1. Popularity, Y. (2019). Yoga Statistics: Staggering Growth Shows Ever-increasing Popularity. [online] The Good Body. Available at: https://www.thegoodbody.com/yoga-statistics/ [Accessed 21 Feb. 2019].

2. Slavich, G. and Irwin, M. (2014). From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin, 140(3), pp.774-815.

3. Bower, J., Greendale, G., Crosswell, A., Garet, D., Sternlieb, B., Ganz, P., Irwin, M., Olmstead, R., Arevalo, J. and Cole, S. (2014). Yoga reduces inflammatory signaling in fatigued breast cancer survivors: A randomized controlled trial. Psychoneuroendocrinology, 43, pp.20-29.

4. Black, D., Cole, S., Irwin, M., Breen, E., St. Cyr, N., Nazarian, N., Khalsa, D. and Lavretsky, H. (2013). Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial. Psychoneuroendocrinology, 38(3), pp.348-355.

5. Buric, I., Farias, M., Jong, J., Mee, C. and Brazil, I. (2017). What Is the Molecular Signature of Mind–Body Interventions? A Systematic Review of Gene Expression Changes Induced by Meditation and Related Practices. Frontiers in Immunology, 8.

6. Harkess, K., Ryan, J., Delfabbro, P. and Cohen-Woods, S. (2016). Preliminary indications of the effect of a brief yoga intervention on markers of inflammation and DNA methylation in chronically stressed women. Translational Psychiatry, 6(11), pp.e965-e965.

7. Mody, J. (2018). Epigenetics and Yoga. Journal of Clinical Epigenetics, 04(02).