David: I've been studying this, as you know, for over 30 years now. And when we first started out, we knew nothing. And then we went to little yeast cells and then we worked our way up to worms and mice. And now, myself and probably a couple of dozen other researchers around the world have broken through a barrier of understanding about why we age and how we can actually reverse it.

Rhonda: Wow. So what's the...

David: Detail?

Rhonda: What's the... Yeah, what's the breakthrough?

David: Well, there were a number of breakthroughs. So in the 1980s, the big breakthrough was that there are...and early '90s, that there are genes that control aging. We call these longevity genes, do not call them anti-aging genes. We don't talk about anti-aging, we talk about longevity and healthspan. And so, these longevity genes were first found in organisms like a nematode worm, tiny little one, and yeast cells that we use for baking in bread and that's where I started my career at MIT with Lenny Guarente running the lab. And those same genes are in our bodies and in pretty much every life form on Earth. And what we've discovered is that when you go for a run or you're fasting, the reason that those are beneficial actually is because they trigger those longevity genes to repair your body and make sure that you don't get as old as you would otherwise.

Rhonda: Just as a sort of a side note, because you mentioned these longevity genes in the yeast and the worms, one of the first... So, in college, I went to UCSD in San Diego and I was a chemistry major. And I worked in biotech. At the time, it was a sort of a start-up, it was Illumina. And I worked in the chemistry department. Now it's a very big company. But I was working there my junior and senior year in college and I, you know, it was sort of like I was making peptides and doing a lot of organic chemistry and after a while, I just didn't feel, like, very interested in it anymore. So I went to the Salk Institute to kind of get a little bit of a taste of biology because believe it or not, I didn't have a lot of biology classes as a chemistry major. Had a few, but it was mostly just, you know, chemistry. And so, at the Salk, I joined Andrew Dillin's lab and...who uses, you know, nematode worms to understand the genetics of aging. And I remember the first time I was working with these worms that had a decreased insulin IGF-1 signaling pathway, how they lived like 100% longer and how they were, like, youthful when they were supposed to be dead. And I saw it with my own eyes when I was doing the experiments and it was like, "Holy crap, this is cool. We have genes that are similar to these little worms and they are like this?" You know, so that kind of got me interested in, at least, on the genetic side of aging.

David: Well, I'm not surprised. Even I don't do all the experiments in my lab, you may be surprised to know. And people would tell me results, "Oh, the mice are living longer downstairs on the NMN," or whatever, or, "We've accelerated aging in mice because we've tweaked the epigenome," and, you know, this all sounds great and, you know, I go back to my email. It's not until I go in to the animal room and I see them with my own eyes, and these are living creatures that are getting older and getting younger. It really is an impact to actually see and hold them with your own hands. So, yeah, that's the thrill. Even with the yeast studies that I was doing back in the late '90s, I was very intimate with the yeast cells. It sounds weird that you could really adore little microscopic organisms, but you look at them under the microscope and they live for about a week and you have to monitor these mother cells and her little daughter cells that you pick up, used to pick off with a microscope and a little pick. You get to know those cells pretty well. You don't give them names, you give them numbers. But when they were getting big, fat, old, sterile, and then they died, you know, it was a little twinge of sadness that these little dudes that you'd been looking after all the time or females, in this case, were dying. So I think, we biologists, we get attached to these living organisms and it's really rewarding to see that we're not making them sick, we actually end up making them live longer and healthier lives.