Rhonda: How stable are these changes in methylation, these methylation patterns that are so-called, you know, the aging clock? How stable are they over a person's lifetime?

Steve: I mean, they are remarkably stable. So, when we compare to any other genomic measurement, I mean, they would be far more stable than anything I'm aware of. They're more stable, far more stable than gene expression, proteomics, metabolomics measurements. All the omics are less stable, you know, and that's really the biological reason why these epigenetic clocks are the most accurate measures of aging. It's just that methylation is so stable. And it's stable not just in vivo, but also when people collect DNA which...So, we've collected DNA, and then we didn't store the blood tubes properly, and so they melted, you know, and we extracted DNA and the measurements were perfect, you know. So, even on a technical level, they're very stable.

Rhonda: That's interesting because I have done experiments, intentionally though, almost the same, where we were collecting blood samples from participants in a trial, and I was measuring DNA damage as biomarked by Gamma-H2AX. And I wanted to know how long I could have blood at room temperature before I started to get artifactual DNA damage happening. And so, I did time course and, you know, found that after two hours of blood being at room temperature, there was just tons of DNA damage had started to increase. That was...

Steve: I see. Yeah. That's scary. That's very scary.

Rhonda: Right? So...

Steve: That wouldn't be the case with DNA methylation. I know because I hired a phlebotomist here in L.A. to visit families to collect blood, and this person didn't have an air conditioner in his car and it was the hottest day in L.A. ever. So, the blood tube melted, you know, that was my experiment. And then I just couldn't send this phlebotomist out to go back to the families to collect blood, you know. I felt sorry for the families. So, that's why we did this experiment, you know, and all I can tell you, we got beautiful data. And so, I see that over and over, and people sometimes ask me, "What if you have a forensic sample?" So, let's say a bloodstain, you know, that was, let's say, in a room for a couple of weeks, or even let's say a bone sample collected, you know, a couple of months later. All of this data, in my opinion, would still lead to very good methylation measurements for the purpose of measuring aging.

Yeah, because it's so stable.

It's just so stable.