Rhonda: Have you measured the epigenetic age in stem cells versus already differentiated cells? Is there a different pattern or different...?

Steve: Yeah. There is a different pattern. So, if you take, for example, a stem cell and iPS cell and then differentiate it into a more mature cell, for example, a more mature neuron, you will find that the epigenetic age increases. The issue is it doesn't increase by a lot, you know, so a more differentiated cell, a more mature cell, it may be one or two years older than the stem cell. The question is, how do we age a cell by 30 years? Because when you study neurons in a dish, you want to perhaps understand neurodegeneration, and so you want to study very old neurons. And so, when you deal with neurons derived from stem cells, we don't have a good way to age them. But nowadays, people pursue this idea called transdifferentiation. So, you take, for example, a skin cell and you add certain factors, maybe microRNAs or what have you, and then turn the skin cell into a neuron, and this transdifferentiation protocol actually preserves the epigenetic age. And so, we have shown in collaboration with several groups that yes, the resulting neuron has the epigenetic age of the skin cell it started with.

Rhonda: Oh, that's interesting. So, what about when you take a skin cell, and you mentioned induced pluripotent stem cells, and you basically can add, you know, like four transcription factors, I think even less now, but the original from Shinya Yamanaka, four transcription factors and make this into like a pluripotent stem cell that can become any type of cell in the body, the epigenome, what happens to the epigenome?

Steve: You completely reset it.

Rhonda: To a young...completely young?

Steve: Completely young.

Rhonda: So, that's like the ultimate reversing aging, right? I mean...

Steve: It's true. Because, in the past, people were wondering, you know, are there interventions that actually reset the epigenetic clock? And the number one proof of principle study is really the administration of these Yamanaka factors because it completely resets the age actually to a prenatal stage, you know.

Rhonda: And that's completely genetic, right? I mean, you're manipulating genes.

Steve: Yeah. I'm not sure. I mean, it's really...So, also messenger RNA can do it, you know.

Rhonda: I guess what I mean is it's something that's kind of under our genetic control, like, ultimately.

Steve: Yes.