Chronologically, I'm 23, but Biologically – I'm 26
Over recent years, I have become somewhat more "conscious" of how I am taking care of my body. Like a lot of people my age, I am not long out of university, a wonderful time of life in which my diet was an ode to "beige" foods such as bran flakes, chicken nuggets and pasta, and my exercise output was limited to the walk to and from my lectures. As for alcohol intake? Well, let's not go there…
Nowadays, the picture is different. I eat a balanced diet, I endeavor to squeeze a run in three times per week, and I practise yoga everyday – almost. Joining the Monday to Friday workforce has meant that alcohol intake is limited to the weekends, and I would say I drink very much in moderation. I consider myself to be a fairly healthy person, to my own standards at least.
But does my DNA tell the same story? In this article, I explore the growing trend of "epigenetic wellness" and put my own DNA to the test, courtesy of Chronomics*.
New ways to measure health?
In medicine, times are a-changing, if you didn't already know. The landscape of medicine is shifting, as scientific technologies rapidly advance and transform the paradigms of traditional medicine. We now have access to biological measures that were previously unattainable, such as our genome.
The term genome refers to the complete set of genes or genetic material present in a cell or organism. This genetic blueprint, inherited from our mother and father, encodes proteins that form the machinery our cells require to function. The blueprint itself cannot be altered. You may hear individuals attribute the status of their health to their "genetics", i.e. "I'm always ill. My mum's the same – it must be our genetics". In some cases, this statement is true. Certain conditions such as genetic disorders or specific cancers result from mutations in our genetic code.
However, there are ways that, as individuals, we can modify the way our body utilizes the genetic code, known as "gene expression".
Modifications to genes that determine whether they are effectively switched "on" or "off" are known as epigenetic changes. The epigenome refers to all of the chemical compounds that have been added to an individual's genome to regulate the expression of genes, with "epi" meaning above; and so epigenetic denotes being "above the genome". You may have read an article published in the Telegraph earlier this year that outlined former Team Great Britain hockey player Sam Quek's adoption of an "epigenetic wellness regime" to help adjust to her life after her retiring from sport.
The article nods to the rise of direct-to-consumer (DTC) genomics, whereby consumers purchase a genetic test from a company and are provided a report outlining the results. At the start of 2018, the DTC personal genomics industry surpassed 10 million genotyped customers.1
But what exactly is epigenetic wellness?
"We live in the era of the OMICS"
Whilst our genetic blueprint cannot be altered, our epigenome can. It can be modified by our lifestyle choices, such as the foods we choose to eat, whether we engage in exercise, whether we smoke cigarettes or drink alcohol. The epigenome can be used to holistically capture the complex state of our bodies at a given time.
Recent epigenome-wide association studies (or, EWAS) have identified epigenetic "markers" associated with many health conditions. These studies have typically focused on gaining biological insights into the disease, but they have not leveraged this information to build disease biomarkers.
Chronomics Ltd, however, are changing the game. Founded by researchers utilizing machine learning to build epigenetic predictors of biological age, they have created the first DTC epigenetic test. They say, "Research and medicine has moved from a concrete biological entity (e.g. a gene, a protein) to entire systems (i.e. all genes - genomics, all proteins - proteomics). We live in the era of the OMICS. Today, this technology is moving out of the lab and into the hands of individuals." I wanted to learn more about the information that can be garnered through epigenetic testing. And so, I decided to dip my toes into "era of the OMICS" by sending a sample of my own saliva to Chronomics.
To accompany my saliva-filled test tube, I am required to complete a self-report questionnaire that asks me various questions about my medical history and everyday lifestyle choices. As I then sit back and wait for the results, Chronomics begin analyzing my sample. "The Science" section of Chronomics' website outlines the rationale behind the methodology adopted in epigenetic testing:
"Today we can measure DNA methylation at single base pair resolution with very high throughput using next generation sequencing technology […]. The most widely used single base resolution methods currently rely on a chemical reaction step called bisulphite conversion. Treatment of DNA with sodium bisulphite enables cytosines to be differentiated based upon whether they are methylated or unmethylated. Methylated cytosines remain unchanged, whereas unmethylated cytosines are converted into the base uracil (U) and then, after PCR amplification (with A,C,G,T deoxynucleotides), into thymine (T). This amplified library (or DNA) pool can then be sequenced and the data processed to map methylation patterns."
Epigenetics of age
A couple of months after posting off my saliva sample and the results are in. Talking me through them is Dr Daniel Herranz, CSO at Chronomics.
First, we touch on the subject of chronological versus biological age. On my last birthday, there were 23 candles on my cake – I've taken 23 glorious trips around the sun. Naively, I assumed this meant that my body was also 23 years of age. Oh, how I was wrong.
Herranz explains, "Biological age, measured using epigenetic data, is the most accurate biomarker of the ageing process in humans. Therefore, your biological age is a much more accurate measurement of your age-associated risk when compared with your chronological age."
In 2013, Professor Steve Horvath of UCLA showed that biological age can be accurately predicted across different tissues using DNA methylation data. Subsequent research has demonstrated that this model is impacted by disease states associated with environmental and lifestyle factors.2
Chronomics take my saliva and assess epigenetic marks at over 20 million positions in the genome to determine the methylation levels. They then look at 1,566 specific positions on my chromosomes that scientific research has shown relate to biological age. My result is generated based on this, along with extra information such as my chronological age, sex, height and weight.
So, biological age is how old my body truly is. 26. Yikes.
"In your case, your biological age is slightly higher than your chronological age. This means that you are aging slightly faster than the average population, probably due to the lifestyle and environmental factors that shape your health," Herranz tells me. Whilst I am somewhat dismayed at this result, Chronomics reassure me that I am aging "nicely", and that "This measurement gives you a good starting point to optimize your health and it is always possible to improve. You can benchmark whether the lifestyle changes and interventions that you undertake from now on are managing to reduce your age-associated risk at the molecular level, and therefore reducing your risk of developing non-communicable diseases (such as some types of cancer, cardiovascular disease, neurodegenerative disease) in the future.
Metabolic status – a closer look at the "molecular BMI"
Next, Herranz runs through my metabolic score, which is classed as "low".
Metabolism is "broadly" defined as the total sum of biochemical processes in living organisms that either produce or consume energy.3 Our genetics, activity levels and diet all influence our metabolic state. Research has demonstrated that chemical tags on our DNA are influenced by the status of our metabolism, and that these tags can provide a better indication of healthy bodyweight than body-mass index calculations.4
Chronomics analyze 113 specific positions in my DNA that relate to my metabolic state. Coupling this information with my self-reported data, my sex, age, height and weight, they generate a metabolic status score. My result of 9% is classed as low.
Bravo! Pushing myself to the brink of near-death whilst running three times a week seems to be paying off.
Herranz explains, "BMI has been traditionally used as a proxy for adiposity and metabolic risk. However, BMI is only a snapshot of your metabolism and does not work well in some cases (e.g. someone that goes to the gym a lot, builds a lot of muscle and weights more, but probably has low adiposity and low metabolic risk)."
He continues: "Metabolic status behaves as your molecular BMI, which is more personalized. The lower the metabolic status value, the lower your metabolic risk. In your case you got 9%, which puts you in the healthy range (i.e. your risk of developing diseases such as type 2 diabetes or metabolic syndrome is low according to your epigenetics)."
Smoke exposure and alcohol consumption
In addition to biological age and metabolic status, the other epigenetic indicators currently assessed by Chronomics in their epigenetic testing approach include smoke exposure and alcohol consumption. We all know that smoking and drinking are bad for us in an array of different ways. But how do they affect our DNA? The 200+ chemicals found in cigarette smoke can induce specific changes in gene expression, and DNA mutations in the liver and the lungs.
Chronomics use machine learning algorithms to determine exactly where on my DNA they need to look for smoke exposure damage. After analyzing 170 specific positions, they determine that only 3% indicate smoke exposure in my DNA, reflective of the fact I am a non-smoker.
I'm intrigued by how these results may differ for an individual that classes themselves as a "social smoker". Herranz tells me, "For a social smoker, we typically observe higher % smoke exposure and higher number of positions with smoke exposure than for a never smoker, but less than for a full-time smoker. Given that the risk associated with smoke exposure is non-linear (e.g. 1 cigarette/day gives roughly 50% risk of developing some cardiovascular conditions when compared with 20 cigarettes/day), the epigenetic test provides social smokers with a tool to quantify their smoke-associated risk, and how it changes over time if they decide to reduce the intake or completely quit."
Next, we turn to alcohol consumption. A plethora of literature now exists that indicates alcohol consumption influences our epigenetics.
For this test, Chronomics look at 110 specific positions in my DNA to predict my cumulative alcohol consumption score. From this information, 101 positions indicated low levels of alcohol consumption. And *breathe*.
"There are several factors that influence this score," Herranz says, "Including the amount of alcohol ingested, how long people have been drinking for and drinking behavior."
It's safe to say that I'm extremely grateful that I chose to partake in epigenetic testing post-university life.
"A high score reflects that your exposure to alcohol may be higher than the recommended national guidelines (> 14 units/week according to NHS) and that this could put you at a higher risk of some diseases (such as liver cancer or cirrhosis)," he adds. "Different types of alcoholic drinks (e.g. wine vs beer vs spirits) might also be associated with different outcomes. Furthermore, other more indirect factors (such as stress and anxiety levels, skipping meals, sleep or exercise) can also affect the final outcome and interventions can be designed in those directions."
Is this the future of personalized medicine?
As Herranz reaches the end of explaining my results, I reflect on what I have learnt about my body through epigenetic testing. On the downside, I'm aging a little faster than I should be. But on the plus side, my metabolic status is low, my body can metabolize the alcohol I consume effectively, and my cells almost seem to be bragging about being smoke-free. But what can I do with this information?
Chronomics intend to support their customers for the long-haul. I'm provided access to my results via a dashboard, where I spy the option to "speak to an expert". Included in the epigenetic test is a free introductory call with a Chronomics health specialist, who can utilize my results to form a long-term health plan. The team encourage you to set health and wellness goals that suit you, and help you track your progression in achieving those goals via regular consultations.
It's true that epigenetic testing has revealed biological insights about my body that I would not have known otherwise, and it has been a fun experience. Focusing on epigenetic changes as a health parameter certainly seems logical, but I'm aware that, as a field in its infancy, there is still a long way to go for epigenetic testing. In terms of future perspectives, I'm intrigued to see whether an epigenetic wellness approach to health and lifestyle will be incorporated into the changing landscape of modern healthcare.
Is this the future of personalized medicine? Let us know what you think.
*Disclaimer: The epigenetic test provided to science writer Molly Campbell was gifted by Chronomics Ltd. Technology Networks are not affiliated with Chronomics Ltd and do not endorse the purchase of their products.
Daniel Herranz was speaking with Molly Campbell, Science Writer, Technology Networks.
1. Kahn and Mittelman. 2018. Consumer genomics will change your life, whether you get tested or not. Genome Biology. DOI: https://doi.org/10.1186/s13059-018-1506-1.
2. Horvath et al. 2016. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease Genome Biology. DOI: https://doi.org/10.1186/s13059-016-1030-0.
3. DeBerardinis and Thompson. Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? Cell. DOI: https://doi.org/10.1016/j.cell.2012.02.032.
4. Tzika, Dreker and Imhof. Epigenetics and Metabolism in Health and Disease. Frontiers in Genetics. DOI: 10.3389/fgene.2018.00361.
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