The Life Extension Advocacy Foundation volunteers recently interviewed Matt Kaeberlein on the topic of the Dog Aging Project, a venture that aims to try in dogs some of the more credible and safe interventions shown to modestly slow aging in mice. When initially proposed, senolytics to clear senescent cells were not in that list, but we might hope to see that change in the years ahead. I'm not overly optimistic about the performance of the other possibilities, such as mTOR inhibitors and other candidate calorie restriction mimetic or exercise mimetic pharmaceuticals. In some cases the evidence is good for these items to work, in the sense of improving health and longevity to some degree, but in general we should expect the effects on life span to be small in longer-lived mammals. All of the mechanisms based on enhanced stress responses, such as those triggered by a lack of nutrients or undertaking strenuous exercise, scale down in their effect on life span for longer-lived species; short-lived species have a much greater plasticity of aging in response to environmental circumstances.
Could you tell us the story of Dog Aging Project? How did it all start?
About five years ago, a new recruit to the University of Washington Healthy Aging and Longevity Institute had recently obtained a small grant to develop companion dogs as a model to understand the genetic and environmental determinants of aging. After a series of discussions, it occurred to me that we had an opportunity not just to study aging in dogs but to potentially develop interventions to delay or even reverse aspects of aging in dogs from those that had already been shown to increase lifespan and healthspan in laboratory rodent models. I decided to focus on rapamycin first, because it was (and still is) the most validated and effective pharmacological approach for increasing longevity in mice, and it has the added benefit that it is effective even when initiated in middle age. After spending a couple of months convincing myself that we could safely perform a rapamycin veterinary clinical trial in dogs, I organized a conference in Seattle in 2014, where I pitched the idea. Soon after that, we started getting quite a bit of media attention, and we decided that we should officially form the Dog Aging Project.
What can you tell us about trials you've already run and their results?
So far, we've only completed one trial, a 10-week, randomized, double-blind, placebo-controlled study of rapamycin in pet dogs. The results of that study were as positive as we could have hoped. We saw no evidence for increased side effects in the dogs that received rapamycin and statistically significant improvements in two of the three measures of age-related cardiac function that we looked at.
Are there any trials you're running right now or are preparing to launch soon?
Yes, the Phase 2 rapamycin intervention trial is currently enrolling dogs. That trial is funded by the Donner Foundation and is a one-year trial to, again, assess effects of rapamycin on cardiac function and to also look at effects on cognitive function and activity. Depending on the outcome of our submitted NIH grant, we hope to begin officially enrolling dogs into the Longitudinal Study of Aging and Phase 3 of the rapamycin intervention trial toward the end of 2018 or early 2019. We hope to have an official announcement on the outcome of that proposal within the next 3-4 weeks.
Can I volunteer my dog for the program, and how do I do that?
Anyone can nominate their dog to participate in either the Longitudinal Study of Aging or the Rapamycin Intervention Trials through the Dog Aging Project website. The Longitudinal Study is currently open to all breeds, ages, and sizes of dogs. The Rapamycin Intervention Trials are restricted to healthy dogs of at least 6 years old and at least 40 lbs in weight.