Steve: Turns out obese people age faster in blood. However, the strongest effect can be found in liver tissue. So, obesity greatly accelerates the epigenetic age of liver tissue, you know.

Rhonda: Have you ever looked at how...So, you mentioned obesity and how obesity is associated with an accelerated epigenetic age. Have you ever come across data with respect to the opposite of that, like fasting or even calorie restriction, if that slows the epigenetic aging?

Steve: Yeah. I mean, in mice, the answer is clear cut. Definitely caloric restriction slows the epigenetic clock in mice. And we know that because several groups have looked at it, including my group. All of us arrived at the same answer. Conversely, by the way, high-fat diet, you know, accelerates the epigenetic age of mice, you know. So, that's all clear cut. The question though is really what about humans? And I'm not aware of a study where people really looked at caloric restriction versus epigenetic aging, but let me share some thoughts. When it comes to any intervention, including dietary intervention that prevents anything related to metabolic syndrome or diabetes, that will be detectable. And also, in other words, if you have an intervention that takes a very obese person to a lean person, in opinion, GrimAge will pick that up. It has to, you know. However, when you ask the question, what about if you take a relatively lean person, healthy body mass index 23, and this person is so motivated to live 10 years longer and they pursue now a lifestyle where their BMI is, let's say, 17, you know, almost at the point of being unhealthy. And so, if you compare a healthy person versus a semi-starved person, would that have a benefit? And, in my opinion, that may not be the case. And I'm just speculating here, but even according to other biomarkers. Personally, I haven't seen convincing studies, you know. Otherwise, I think my by BMI would be 17 right now.

Rhonda: That's the question. It's like, well, if you have these types of interventions on already healthy people, will they make any difference? At least according to epigenetic aging, right...