Eat your vegetables. Stay active. Avoid smoking. Keep out of the sun.
Patients have been hearing this good advice from their doctors for a long time. Now, researchers are uncovering new evidence that our lifestyle choices – the foods we eat, the chemicals we encounter, our exercise habits and even our social connections and emotional states – can measurably influence mortality risk at a genetic level.
The emerging science of epigenetics potentially promises to influence clinical practice and insurance risk selection, according to Dr. Daniel Zimmerman, Senior Vice President, Chief Medical Director, Global Support Team for RGA. With a background in molecular biology and medical microbiology, Dr. Zimmerman is board-certified in internal medicine and pediatrics and has more than a decade of experience in insurance medicine. We sat down with Dr. Zimmerman to discuss epigenetics and the opportunities and risks ahead.
This post is the first in a two-part interview with Dr. Zimmerman based on his webinar “Epigenetics and Liquid Biopsies: Fact, Fiction or Both.” Read Part II here. RGA's medical team has also published an in-depth white paper on liquid biopsies, available for viewing and download here.
Epigenetics is the study of how molecular changes in the backbone of our DNA influence how our genes function. We’re not talking about changes to the core sequence of our genetic code, the ordering of base pairs of A,T,C, and G nucleotides that make up the double helix of DNA. This code remains unchanged. “Epi” means “on top of” in Greek; this is the study of how certain environments or experiences can induce processes that change how our genetic codes are expressed – turned off or turned on. Our choices can subtly influence gene activity in ways that are correlated with all-cause mortality.
Think about it this way: Have you ever celebrated a birthday, and somebody tells you, “Well, age is just a number”? For example, two men celebrate turning 50 years old, and yet one may look 40 and the other might look 60. Why? We know obesity, smoking, and other lifestyle decisions, as well as heredity, can influence the appearance of age. And the idea that your chronological age may not align with your biological age is now becoming more understood.
Genetics vs. epigenetics – what’s the distinction?
There is a very real difference between genetics and epigenetics. If nothing else, carriers should understand that our genes are not changed by lifestyle or environmental factors; however, these factors can influence how our genes are activated – or silenced. That’s really what distinguishes genetic variation from epigenetic variation and why epigenetic alterations are reversible.
What should insurers understand about the biochemical mechanisms that alter or influence gene expression?
There are three areas of epigenetic study: DNA methylation, histone modifications, and higher-order chromatin structural modifications. DNA methylation involves molecular changes that may occur in response to environmental factors: the foods we eat, the chemicals we come into contact with every day, the viruses we contract, and our level of activity. There is something called a methyl group, a biochemical structure of carbon and three hydrogen atoms, that can be added or subtracted to one of the nucleotides that makes up our DNA – C or Cytosine. Now remember we're not changing the cytosine or the overall order of where C appears in our DNA base pairs of A,T,C and G. But by adding a side chain of a methyl group through methylation, a gene could be turned on, or more commonly turned off.
Think of histones as a spool – DNA is basically wound around this protein structure, rolled into a nucleosome, and then combined to assemble a chromosome. Methylation can occur to this spool, making it less sticky and allowing the DNA to become exposed and activated in different ways.
Higher-order chromatin structure refers to the entire strand of the DNA and the nucleotides all together. Different parts of this DNA strand can come in contact with each other; this physical contact can sometimes result in certain genes turning off or on.
How do environmental or behavioral factors trigger these changes?
Much more work needs to be done to understand specific changes that are occurring in the genes exposed to different environments and lifestyles. We know diet and nutrition impact epigenetics, as do chemical exposures such as tobacco and alcohol, medications and drug abuse, and even pollution. Exercise, stress, depression, and other chronic diseases and viral infections can also play roles. We believe some of these influences can begin in utero, but there is much more to learn.
With so much more to study, how can we know if epigenetics will eventually prove predictive of mortality?
Impressive research in the last few years already correlates epigenetic changes with outcomes and all-cause mortality. I explain this in more detail in my video, but some scientists have identified an “epigenetic clock” – like a biological clock that can measure variations in the aging process. Studies of identical twins are also revealing significant insights into biological versus chronological age.
This is a very exciting field of study, and the underwriting implications can’t be ignored. We may be able to assess behavior with a test – smoking for example. Insurers currently rely on a cotinine test to determine if an applicant smokes. An epigenetic test may be able to actually quantify the physical effect of smoking. Perhaps one day carriers could routinely test to determine how many cigarettes a day an applicant might be smoking and whether he or she quit a week ago to influence a blood test.
Talk a little bit about epigenetic testing and what the future might hold for insurers.
If some forms of epigenetic testing ultimately satisfy regulatory standards, one could imagine a number of potential benefits. We could utilize epigenetic information to improve life risk stratification or the design and product offerings of impaired annuities. We also need to consider opportunities as part of wellness initiatives: Could there be a post-issue benefit offered to clients, in which epigenetic testing becomes a part of a program to help insureds make better lifestyle decisions? All of these considerations may have seemed like science fiction a few short years ago; now they are closer to becoming science fact.