Steve: The Horvath Aging Clock is what I sometimes call the so-called pan tissue epigenetic clock. And so, it is the most accurate molecular measure of age. It applies to all cells in the bodies. Certainly, all cells that have DNA, all tissues, all organs. It measures age in prenatal samples, in children all the way to supercentenarians, people who are over 110 years old. And it measures age. So, if somebody provides, for example, DNA from blood, or DNA from neurons, or DNA extracted from saliva or urine, I can very accurately estimate their age.

Rhonda: Their chronological age, like how old they are in years?

Steve: Exactly. And that's already a deep question. So, the clock does measure chronological age. However, it's of course, not a perfect measure of chronologic age. There's always an error. For example, if I analyze the blood from a 50-year-old, the epigenetic clock may say well, this person is actually 55 or 45. And so, there is a small error, and this error is actually biologically meaningful, you know. It's not just noise, but rather it is in part related to what people call biological age.

Rhonda: That's super interesting there, that basically the error was actually related to biological aging because that was the next thing I was going to say was, you know, people age at different rates, like even, you know, obviously chronologically they could be the same age, but if you look at a variety of biomarkers...In fact, there was a paper published a few years ago in "PNAS" that looked at, like, 18 different biomarkers. They looked at glycated hemoglobin, so HbA1c, VOâ‚‚ max, triglycerides, telomere lengths, immunosenescence, a lot of the, you know, typical biomarkers that are clinically used to, like, determine health status. And it was basically found that people, you know, aged at very different rates based on those biomarkers. So, some people biologically appeared much younger than their chronological age, and some people appeared much older than their chronological age. So, now you've developed a different clock that can actually predict...

Steve: That's right. Well, let me comment first on the term biologic age. It's a very intuitive term. Most people have a vague understanding of it. It somewhat relates to morbidity risk or mortality risk and also aging. But strictly speaking, it's not well defined because different researchers have different ways of measuring biological age. Some people use clinical markers that you mentioned, various markers of glucose levels or lipid levels, and so on. Now, my take to measuring biologic aging is based on a chemical modification of the DNA molecule. It's DNA methylation, you know. And I mention it because depending on how you measure biologic age, you might get different answers. So, a person might look bad in terms of glucose levels, and you would say, well, they age faster than they should. However, it could turn out that according to methylation, they are actually in pretty good shape, you know. So, yeah.

Rhonda: Have you seen that before where you can see people have, for example, like other clinical biomarkers that are unhealthy like higher fasting blood glucose or maybe elevated triglycerides, elevated C-reactive protein, a marker of inflammation? Do you find that those typically correlate well with the epigenetic age or...?

Steve: I wouldn't say it correlates well. It correlates, you know, so people who have high levels of inflammation and what you mentioned, the epigenetic clock goes a little bit faster, but the word is there's a weak relationship, you know, because it is quite possible that somebody turns out to be in good shape according to epigenetic aging rates. And the number one example I want to mention in this context are actually people of Hispanic ancestry. Unfortunately, Hispanics often have a higher risk for diabetes, the higher metabolic syndrome. However, according to the epigenetic clock, they actually age more slowly, you know, and so there is this really this disconnect. And this is actually an interesting disconnect because there's something known as Hispanic mortality paradox, you know. Hispanics, as I mentioned, have often a disadvantageous risk profile according to clinical biomarkers. But it turns out, on average, they live much longer than expected. They actually live longer lives than people of European ancestry, you know. And that association is paradoxical to a clinician who looks at clinical biomarkers. But according to the epigenetic clock, it's not paradoxical because, as I mentioned, we have found that Hispanics age more slowly according to the epigenetic clock.