What about the differences in hormonal levels? I understand that most adults in the United States are neutered. So that makes them castrated irrespective of their sex. I certainly in New York, dogs don't bark. I'm sure it's part training. But that's probably has to do with the fact that they're neutered, whereas in other parts of the world, you know, they mostly are not. And I can attest, they certainly bark. So how do you control for those hormonal varieties? Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. 

Yeah, so really good question. I would say the first real answer is we don't even try to control it. We want to capture that variety. Right. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. So the whole point of a longitudinal study is to get as much of the genetic and environmental diversity as we can to try to then figure out, you know, what are the strong correlations. But you're right in our cohort, which for now is restricted to the United States, the majority of dogs, I think it's in the 80 to 90% range are sterilized. And so, we are overrepresented, certainly for sterile dogs. But having said that, particularly among purebred dogs, there are a significant fraction of dogs that are not sterilized, and so they go through their entire life intact. And so we can do, we can ask questions about the relationship between sterilization status and age-related health outcomes because we've large numbers of both types of dogs. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. And I will say there have been prior studies, some of which have been done by members of the dog aging project team, Daniel Promislow and Kate Creevy, and others looking at this question. And it's interesting because it seems as though when you control body size. Hence, the body size is the greatest predictor of lifespan in dogs when you control for that, dogs that are sterilized do have a slightly longer life expectancy. But what's potentially more interesting is the diseases that that sterilized dogs die from, or at least which are associated with death. Sterilized dogs are somewhat different than the spectrum of diseases that intact dogs die from. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. So I think the take-home message is, yeah, you know, sterilization and hormonal changes with age play a role in the risk of certain diseases with age, the extent to which they affect the underlying biological aging says, I think is a different question. And one that's a little bit less clear. So. So I think it's important and it is absolutely something that we're aware of a couple of points to make, you know, I think it's funny, because when you talk to the average person, certainly, they're aware that dogs are sterilized, typically in the United States, but they don't appreciate the fact that that sort of creates four unique sexes and companion dogs in there are intact males, intact females, sterilized males, and sterilized females. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. And I think it's important to appreciate that, you know, when you sterilize an animal, there are pretty substantial changes in the hormone, hormone sex hormones in particular, which really, fundamentally change the biology of that animal. And so we are very aware of that. And, you know, always pay attention to the role that sterilization and sex could have on different age-related health outcomes.

Oh, that's certainly very interesting. That's, that's a fascinating, true animal model that probably approximates the human life, you know, more than some other models do. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD.