#489 Inside the Dog Aging Project: What It’s Teaching Us About Longevity - Dr Daniel Promislow

Daniel Promislow (0:00)

Because everything is sped up in dogs, and if we find that there appears to be a risk factor in the environment that's increasing on a particular kind of cancer, for example, we can then do a deep dive into people in that environment in a targeted way and ask if there's a similar risk for people. Dogs that feed just once a day are also dogs that tend to have lower instances of gastrointestinal problems, pancreas problems. But there's an interesting challenge here.

Siim Land (0:27)

Dr. Daniel, welcome to the show.

Daniel Promislow (0:30)

I'm really pleased to be here. Thanks for asking me.

Siim Land (0:33)

Yeah, I'm excited to have you on the show. Now, my podcast often talks about longevity and extending human lifespan, but extending dog or a companion dog, a lifespan is also something I think a lot of people care about, especially dog lovers, and you are involved with a very interesting project, which not only might help to extend dog lifespan, but the lessons we learn from there might also be applicable to humans as well. So I'm very excited to dig into the research that you're doing. But yeah, maybe we can start with what is the Dog Aging Project, and how did you get involved with that?

Daniel Promislow (1:14)

The Dog Aging Project is a long-term longitudinal study of dogs all across the United States. We have enrolled over 51,000 dogs since we launched in 2020 And these are companion dogs or pet dogs in people's homes. And most of what we do for our research is observational. So we collect a lot of data, massive amounts of data, which we then use to understand what makes some dogs healthier agers than others. Why do some dogs stay healthier longer than others? What are the environmental factors, the genetic factors, the biological factors, and what are the underlying mechanisms by which genes and environment influence how long a dog lives? And then about 1% of the dogs in the study are also enrolled in a clinical trial to see if rapamycin can increase healthy lifespan in dogs. And how it got started is a bit of a long story, and I'll try and be brief.

So, way back in 2007, a paper came out on size in dogs from Elaine Ostrander's group. And in humans, if you think about the genetics of size, there are probably hundreds of genes that each contribute a tiny little bit to determine overall whether we are average height or taller or shorter than average. That's true in dogs as well, but there's one gene in particular which accounts for about half of the variation in size. If you have one form of that gene, if you have two copies of one form of that gene, you tend to be a toy breed. And if you have the other form in two copies, you tend to be a giant breed. And that gene is IGF-1 or insulin growth factor one. When that paper came out, I was immediately excited because we know that the pathway that that gene acts in IGF-1, insulin signaling, is thought to be important for aging in many different species. In the lab, in mice, and worms, and flies, and possibly even in humans. And so that paper came out and immediately I wanted to answer the question of whether that gene is the reason that we see this really striking pattern in dogs that's different from what we see across species, which is that the large breeds are shorter lived than the small breeds. And we're still trying to answer that question and a million other questions. And that led to creating this project with my co-founders, Kate Creevey, who's now at Texas A&M, and Matt Caberline, who was at the University of Washington when I moved there, and now is CEO of a company OptiSpan. And we continue to work together.

Siim Land (4:06)

Yeah. Yeah, that's very interesting. This relationship between body size as well as in humans is also related to height, of how, yeah, like a shorter, I guess. So it's interesting that I think the relationship is that larger species tend to live longer than smaller species, but smaller individuals in that species live longer than the larger individuals. So like whales live longer than mice, but smaller whales tend to live longer than larger whales, if that's correct, or like humans. Larger humans tend to live shorter and shorter humans, but humans live longer than the mice, for example.

Daniel Promislow (4:49)

Yeah. So the clearest pattern is actually in dogs. There's a two-fold difference between really long-lived breeds like a Toy Poodle or a Havanese, and then a very short-lived breed like a Great Dane, for example. They differ in size by, could be 50-fold and in lifespan by two-fold.