Dr. Steve Horvath is an aging researcher and bioinformatician whose research lies at the intersection of epidemiology, chronic diseases, epigenetics, genetics and system biology. He works on all aspects of biomarker development with particular focus on genomic biomarkers of aging. He developed a highly accurate multi-tissue biomarker of aging, known as the “Epigenetic clock”, or “Horvath’s clock”.
We will start with some basic definitions: What is epigenetics? Why is it important and what is the correlation between epigenetics and aging?
Dr. Horvath: Epigenetics refers to chemical modifications of the DNA molecule. These epigenetic changes are known to be crucial in human development. For example, as a fetus develops, or as a cell is determined to become a liver cell or a skin cell, they need these epigenetic changes to inform cells of their identity and what kind of cell they are. But research by many aging researchers indicates that epigenetics also plays a very important role in the aging process. There are different kinds of epigenetic changes. My own interest lies in a special kind of epigenetic change known as DNA methylation. The reason I studied DNA methylation is that it relates very strongly with aging across the entire life span. It also plays a role in the aging processes of many tissues and cell types of the body. DNA methylation can be robustly measured, and it is very easy to measure. This is why my lab focuses on using DNA methylation, to develop ways of measuring aging, and also ways of predicting life span or risk of various diseases.
What is the difference between Horvath’s clock and the GrimAge clock, which was discovered by your lab early this year?
Dr. Horvath: We developed different kinds of epigenetic clocks for different purposes. My original publication from 2013 described a clock that works in all tissues and cell types. You can apply it to neurons, to skin cells and blood, any source of DNA. However, this original clock is not the best way of predicting life span or the time you have or your health span. Therefore, in my lab, we continued to develop better predictors of life span. And our most recent clock, which we named after the Grim Reaper is called “DNA Methylation GrimAge”. Although we only published it a few months ago, I have already received enthusiastic feedback from the aging community. People tell me that this methylation-based predictor validates in their own epidemiological cohort data. Therefore, I'm quite optimistic that this “GrimAge clock” will be useful for people who want to study the effects of antiaging interventions, including lifestyle interventions.
We have biomarkers that could be used today to judge the potential of antiaging intervention.
Despite enormous progress in age science, there is still no set of agreed-upon biomarkers, and as a result, no standard way of quantifying biological aging. Without that, it is difficult to assess the effectiveness of age-slowing treatments and to attract more funding for innovations to slow down or even reverse the aging process. How far are we from succeeding in this area?
Dr. Horvath: I agree with you that there are still a lot of debates on how to measure biological aging, we probably need several different kinds of biomarkers. For example, on the one hand, we need biomarkers that measure clinical disease, almost a traditional measures of glucose levels in blood, or blood pressure for hypertension, or many other biomarkers that the doctor evaluates during a physical check, for example, blood cell counts. But beyond these traditional biomarkers that are ready for use, we also need molecular biomarkers. For example, we do need an epigenetic clock, in my opinion. So the good news is: we already have biomarkers that you know, we have biomarkers that could be used today to judge the potential of antiaging intervention. Having said this, it's always good to develop additional biomarkers. Fortunately, this has become a very active area of research. There are many labs working on this problem, and also the National Institute of Health in the U.S. dedicates research funding for that area. I have a very positive view. On the one hand, we have very good biomarkers already. On the other hand, I expect improved biomarkers in the future.
Is there any treatment that is directly addressing DNA methylation?
Dr. Horvath: We do not have effective interventions for humans right now. There are lifestyle factors. For example, smoking, which is a bad habit, does negatively affect your methylation level, and it increases the grim age. So on that level, you could have an easy intervention - stop smoking. However, when it comes to more drastic measures, for example, trying to rejuvenate you by 10 or 20 years, we do not have such an intervention for humans. However, we do have interventions that work in mice, for example, the procedure for generating stem cells out of adult cells. These are the so-called Yamanaka factors, that can be used to reprogram cells. And this kind of intervention greatly reduces the epigenetic age of cells. So one could think of modifying this procedure so that it is less toxic, and maybe adapting it for the case of humans. But overall, I think this is a very active research field, my group works on, and I am quite optimistic that within a couple of years, there will be interventions that apply to humans that reset the methylation age.
What is your own recipe for healthy longevity?
Dr. Horvath: Well, I simply do what everyone else does, I exercise regularly, I stopped smoking, I try to avoid diabetes by not eating too many sweets - just the boring lifestyle recommendations that everybody knows about. They are boring, but they are clearly the most effective. Even our epigenetic clock study revealed that. So when we have applied grim age, to study lifestyle behaviors, we have definitely noticed that people who eat vegetables age more slowly, at least their blood ages more slowly. It is similar in people who smoke, they age much faster. People who are obese also age faster. Everything we know about healthy lifestyles is actually confirmed by the epigenetic clock.
Dr. Horvath thank you very much for speaking to us today.
