Rhonda: What about...So disease stage, you mentioned cancer. People with cancer or Alzheimer's disease or Parkinson's disease, like, have you measured the epigenetic age of these individuals and does it look like it's accelerated aging?

Steve: Yes. So, we looked at blood samples from Parkinson's cases and controls, and there's no question, there's an age acceleration effect in blood. It's minor. It's one or two years, you know, but it is there. Alzheimer's disease, we looked at prefrontal cortex samples from the Religious Order Study, you know, and again, we found age acceleration in the prefrontal cortex. When it comes to blood samples from Alzheimer's disease, I think there might be a signal, but if there is a signal, it's very weak. And also...what other disease did you mention?

Rhonda: Cancer.

Steve: Cancer. Yeah.

Rhonda: I'm wondering...you know, cancer is a beast. I mean, there's so many different types and...

Steve: Yeah, cancer is complicated. So, the exciting insight is that yes, blood methylation data indicate that blood samples collected before the person develop cancer show a slight epigenetic age acceleration. So, that supports the view that faster epigenetic aging is predictive of future onset of cancer. And that finding has been validated by many groups. Problem is this association is weak, you know, you need really a couple of thousand people to observe it. But the question is, what about if we, for example, measured...?

Rhonda: Tumor tissue.

Steve: Well, tumor tissue, the signal is huge. So, for example, when I analyzed malignant breast tissue samples from women with so-called luminal breast cancer, the epigenetic age acceleration is off the chart. So, their breast tissue is much older than expected. But it's complicated because...

Rhonda: Have you compared it to their blood? Like, is tumor tissue the same?

Steve: No, no. It would be different. I mean, I would say the...I mean, yeah, let's say in breast tissue we find 10, 15 years age acceleration in malignant tissue, but in blood, I mean, the effect would be much smaller if at all.

Rhonda: It's very interesting because you mentioned Alzheimer's disease blood also...

Steve: Very weak effect.

Rhonda: ...very weakening signal, but if you measured actual brain tissue, which is where, you know, it's a neurological disorder and find a signal, the interesting thing is you said Parkinson's disease, you do measure the signal in the blood.

Steve: Yes, that's true.

Rhonda: It'd be really interesting to know if the immune system is playing a role in Parkinson's disease.

Steve: I can tell you the following. So, we did this study of Parkinson's people. Why? Because I was interested in epigenetic aging. However, my software also produces estimates of blood cell counts. And so, it turned out that the blood cell counts, in particular neutrophils, were really highly elevated in Parkinson's disease, huge effect, you know. And so, in certain ways, this was completely surprising to me, but this finding has now been validated over and over. So, yes, PD cases have highly elevated neutrophil counts.

Rhonda: That's very interesting.

Steve: Yes. So, yes, immune system plays a role. We don't know the causal direction, you know, is it first immune dysregulation that gives rise to PD or is it the other way around?

Rhonda: There's been some interesting links to gut, the relationship of gut and Parkinson's, and of course, the immune system's involved in the gut and all that.