Regina Onishchenko ’18 and Allie Richey ’18
Ironically, in a world that is exploding with new technology, more and more individuals are feeling increasingly disconnected with others and with themselves. As Anderson Cooper stated on 60 minutes, “I’m on mobile devices all day long. I feel like I could go through an entire day and not be present. It’s exhausting”11. As a way to remedy this disconnection with oneself and relieve everyday stress, mindfulness-based practices have been on the rise, especially in workplaces and hospitals. Mindfulness-based stress reduction (MBSR) practices are techniques that help individuals self-manage worrisome, intrusive thoughts1. A few examples of well-known mindfulness-based practices include yoga, sitting/walking meditation, repetitive prayer, and other therapeutic practices that allow an individual to become more aware of their own physical and mental condition in that particular moment.
While there are many skeptics of this type of “medicine,” we hear stories of medical patients who have greatly improved their symptoms by using some of these techniques. Although some consider it to be a miracle, these stories make us question the role of this type of practice on the body. For example, take the recent case seen at Duke University, where a woman diagnosed with stage four breast cancer enrolled in an eight-week MBSR program. This patient had such high anxiety that she couldn’t go more than five minutes without worrying about her family. After just two short months of therapy, she was able to focus on other things for days at a time without having constant anxiety8. Could mindfulness based practices like meditation or yoga actually be altering the way our bodies work, simultaneously increasing our resilience to disease while fighting mental disorders? While it’s still early, emerging research has shown us that this may in fact be a possibility. Mindfulness based practices can actually change the way our genes are expressed, and this can play a beneficial role in our overall mental and physical health.
Before we can explain the ways in which mindfulness based practices change our brain and body, we first need to explain the biological mechanisms behind this idea. Think of the human body as a long play. The smallest units of our bodies, the cells, play the actors and actresses. These “actors” are all following a biological “script”, which we call DNA. “Genes” are specific lines of the script that direct the actors’ actions through their scenes. Each cell in our body contains the same exact DNA “script”, regardless of whether it is an eye cell, heart cell, or toe cell. But why are these cells so different if they contain the same exact script? The answer is something called epigenetics. The role of epigenetics is to function as the director. While the actors and script stay the same, the director has the ability to change the production by altering who’s on stage at what time, or by modifying the way each actor reads his or her script. Putting this in terms of our body, each cell has the same DNA, but not every gene or instruction is directed to be “on” in every cell due to various epigenetic mechanisms. So, for the eye cells, only the “eye” genes are expressed, while the “heart” genes are silenced. The expression of different genes, known as “gene expression,” is the driving force that makes each cell type unique. It is what gives each and every cell in our body its own job. Determining which genes are “on” or “off” in each cell depends on whether the epigenetic director has modified that cell’s script, and where exactly the director may have made changes.
There are different ‘tags’ on the DNA script that decide whether or not that gene should be accessed. Some of these ‘tags’ were given to us when we were born while others are given to us from the environment we live in, the food we eat, and the interactions that we have with others. These environmental tags are called epigenetic marks. Once the DNA is tagged, there are a variety of different mechanisms through which specific genes will be expressed or silenced, depending on the chemical makeup of the tag. In terms of the play, the director can mark up the script so certain lines or scenes are included or excluded. For example, they can be highlighted, crossed out, or underlined.
This is where mindfulness based practices come in. A number of recent studies have looked at differential gene expression before and after mindfulness based practices to see whether they provide health benefits, therapeutic potential, and epigenetic changes to our genomes. Across observational trials, cross sectional studies, and experimental studies looking at the beneficial effects of mindfulness based practices, there have been a few epigenetic outcomes that stand out. These include decreased NF-kB -related pro-inflammatory gene expression (basically, the expression of genes that cause inflammation and often make diseases worse), downregulation of HDACs (histone deacetylases), and differentially methylated regions of the genome. Don’t worry, we’ll explain what all of these mechanisms in the next few paragraphs.
The Nf-kB genes are pro-inflammatory genes that are part of a pathway involved in the inflammatory stress response. In a multitude of psychiatric illnesses, including clinical depression, gene expression levels of pro-inflammatory genes are increased or “upregulated.” 3. A study conducted by David Black and colleagues explored the effects of yoga and meditation on expression levels of pro-inflammatory genes and antiviral genes (genes that reduce the ability of harmful viruses to survive and replicate in the body) in family dementia caregivers2. To do this, they randomly assigned individuals from a group of 39 caregivers to either practice Kirtan Kriya Meditation (KKM) for twelve minutes daily for eight weeks or to listen to relaxing music for the same amount of time. KKM is “a yogic meditation chanting practice guided by a CD,” that is done at the same time every day. It takes twelve minutes to complete and consists of silent focus, finger movements along with chanting, then deep breathing and visualization of light2.
After eight weeks, they examined each person’s DNA to look for changes in gene expression between the groups. They found a decrease in expression of pro-inflammatory genes and an increase in expression of antiviral genes in the meditation group compared to the relaxing music group. Since caregivers of people with dementia have previously been found to have worse mental health and a poorer immune response than controls, these results demonstrate a possible benefit of meditation on the health and immune capabilities of these individuals.
Moving forward, another type of epigenetic mechanism that mindfulness based practices has effects on is something called “histone deacetylation.” Histone deacetylation is a mechanism that removes a type of epigenetic “tag” known as an acetyl group. This biochemical process is done by enzymes, tools that make the cell function, known as histone deacetylases (HDAC), whose primary role is to remove acetyl groups from groups of proteins known as histones. When the acetyl groups are removed, the histones will tighten their grip on the DNA, prohibiting protein-building machinery to access the DNA. Returning to our analogy, if the DNA acts as a script in the play, the histone deacetylases act as markers that cross out portions of the script so that the actors and actresses know not to include that specific scene in the play. Enzymes act as all the various tools that you could use to highlight, underline, or cross out various scenes in the play.
In 2013, Perla Kaliman and her research group analyzed the effect of intensive mindfulness meditation on epigenetic changes to genes in the bloodstream7. A group of 40 individuals, 21 participants that were new to meditation and 19 long-term meditators, were studied before and after an intensive day of mindfulness meditation or leisure time. The control group was engaged in activities that didn’t include mindfulness practice while the long-term meditators engaged in mindfulness based activities such as an inspirational meditation talk, a guided siting practice, and a guided walking meditation. In addition, participants completed the Trier Social Stress Test (TSST), an acute psychological stress test, to look at the association of a lab-induced stressor on which genes are “on” and “off”.
They found that after the intervention, the meditation group showed a decrease in the expression of histone deacetylases: HDAC2, HDAC3, and HDAC9, the substances in the body that act as the markers to cross out portions of the script. Upon evidence that meditation can modify concentrations of HDACs, the researchers decided to investigate whether there was relationship between these decreased HDAC levels and expression of pro-inflammatory genes. They saw a significant decrease or “downregulation” of pro-inflammatory genes in the mindfulness meditation group. These findings show that, “an intensive day of mindfulness meditation seems to trigger an anti-inflammatory response that is not observed after the same period of time in controls.” 7. Moving further, they looked at cortisol (a stress hormone) recovery levels from the TSST at the very beginning of the study and then again twelve weeks later to see if the genes that they previously found to be differentially expressed could predict cortisol recovery. They found that lower levels of HDAC2 and pro-inflammatory genes were associated with better cortisol recovery, meaning that the meditators could bounce back from stress more easily. These observations, taken together, could potentially explain the underlying reason that this epigenetic regulation that is influenced by meditation could have therapeutic benefits.
Interestingly, another study lead by Dr. Javier García-Campayo revealed epigenetic regulation of genes involved in common diseases through an entirely different mechanism than was previously mentioned5. Remember, we previously said that the way the environment controls gene expression depends on the chemical makeup of the tag it puts onto the DNA or histone proteins, like the way marking up the script (crossing out, highlighting, etc) changes the way the actors and actresses portray the scenes. Well, the type of tag these researchers were looking at is one that adds methyl groups directly to the DNA, which act to block the DNA from being read. Similar to our previous analogy, the methyl groups act as red pens on the script. They decrease the visibility of the lines to ensure that the actors and actresses can’t get access to these specific lines in the scene. In this study, the researchers analyzed each person’s DNA to look at differentially methylated regions (DMRs) on the DNA of white blood cells (cells involved in the immune response and combating diseases) in 17 long-term mindfulness meditators as well as 17 members of a control group, which consisted of family or friends of the meditators who lived a similar lifestyle. They found 64 differentially methylated regions in the meditators as compared to the controls, which were associated with 43 different genes.
In most of these regions (45 out of the 64), the DNA was hypomethylated, meaning that there was less methylation, and the protein-building machinery could access these genes more easily. They then wanted to see if these 64 DMRs were related to genes that are involved in certain human diseases, and they found that of the 64, 16 DMRs were located in genes associated with neurological or psychiatric diseases, and 15 DMRs were in genes involved in cardiovascular or immune diseases as well as cancer. The results from this study show a correlation between long-term mindfulness meditation and methylation changes in specific genes involved in common human diseases, as well as biological and cellular processes, that could influence our body’s immune response to harmful germs.
Over the past twenty years, we’ve seen an exponential increase in the prescription of SSRIs, SNRIs, and many other medications for clinical depression. While experiments have shown a biochemical route of action that is beneficial to some patients, there are many unwanted side effects that come with taking these drugs. This has lead individuals to explore alternative routes, including mindfulness based practices, to help alleviate symptoms of many human diseases. Although the research is still very new, there is substantial evidence that mindfulness based practices, such as yoga and meditation, have the ability to change the way our cells perform on a daily basis. We hope that research continues on meditation based practices and their therapeutic role in health and wellbeing, and that causal relationships can be identified. We believe that the art of mindfulness based practices can have the ability to not only help center oneself, but improve overall mental and physical wellbeing through various epigenetic mechanisms such as histone deacetylase, DNA methylation, and gene expression of pro-inflammatory genes.
References
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