How metabolic dysfunction shapes aging in dogs

In this video, Brennen McKenzie, MA, MSc, VMD, director of veterinary medicine at Loyal—a biotechnology company focusing on extending the healthy lifespan of dogs—explores the complex biological drivers of canine aging, focusing on metabolic dysfunction as one of Loyal’s special areas of interest. He notes that as dogs age, their energy metabolism becomes less efficient, leading to internal changes such as decreased insulin sensitivity and elevated insulin levels, which can increase the risk for cancer or dementia.

The following is a transcript of the video, lightly edited for clarity and cohesion:

McKenzie: I'm Brennen McKenzie. I'm a small animal veterinarian, and I am currently both part-time in private practice, where I've been for almost 25 years now, and also the director of veterinary medicine for Loyal, which is a biotechnology company based in San Francisco, [California], and our mission is developing medications to try to extend the healthy lifespan of dogs.

dvm360: What are the main biological mechanisms that drive aging and age-related disease in dogs?

McKenzie: There are many mechanisms. Most of them, or a lot of them, have been collected in a little scheme called the Hallmarks of Aging, which is widely used as a way of, sort of, organizing the complicated biology of aging into categories that make it easier to investigate, to look for new therapies.

One of the ones that we're particularly interested in at Loyal is something called metabolic dysfunction. As people and dogs get older, our energy metabolism gets less efficient. And you know, we all know that; I used to be able to eat whatever I wanted, and I never gained weight, and I felt great, and now, at my age, I can't do that anymore.

So, that involves internal changes: things like less sensitivity to insulin, which makes our insulin levels go up, and that can drive risk for cancer or for dementia. Changes in our blood lipids—you know, we all get high cholesterol as we get older, and in humans, that tends to lead to things like heart attacks and strokes. It doesn't cause that in dogs, but it causes other kinds of health problems in the same sort of way.

So, metabolic dysfunction is, in particular, one of the mechanisms that we're interested in because it's something that we've seen success in treating in a variety of ways.