Researchers from the University of Arizona College of Veterinary Medicine are investigating an interesting phenomenon they encountered studying how dogs age: while large breeds tend to live shorter lives than their smaller compatriots, their brains seem to age at the same speed.

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"Based on their different lifespans, you might expect large dogs like Great Danes to develop signs of dementia around 8 years old, but small dogs like Chihuahuas to have a later onset – somewhere in their teens," said Evan MacLean, associate professor of veterinary medicine. "But that's not what we find. The implication is kind of interesting: It means that big dogs may just die before they acquire any kind of cognitive dysfunction."

To better understand the biological mechanisms that drive aging, MacLean will soon launch the Study of IGF‑1, Neurocognitive Aging and Longevity – also known as SIGNAL. The project will investigate how the growth hormone IGF‑1 influences cognitive aging in dogs. The research aims to determine whether dogs of similar size age differently depending on circulating levels of IGF-1. 

The study is supported by the American Kennel Club Canine Health Foundation and will include 75 medium-sized dogs from the local community. MacLean and his colleagues will track the animals' hormone concentrations through blood samples and combine that data with a series of in-person cognitive assessments performed over the course of two years.

MacLean, who also leads the Arizona Canine Cognition Center, hopes the study can eventually lead to a better understanding of cognitive aging in humans.

"Animals play a huge role in all kinds of medical research, but that often happens with mice kept in artificial laboratory conditions," MacLean said. "Their world is much different than our own, and these mice are often clones of one another so there is no genetic variance. Companion dogs on the other hand are much more genetically diverse, share our world in very meaningful ways and receive high-quality medical care throughout their aging."

Observations and community collaboration

Investigating the IGF‑1 hormone, also known as insulin‑like growth factor 1, began like many scientific pursuits: with an observation. Large dogs tend to have much shorter lives than small dogs, but why is that? Conventional wisdom would suggest they just age more rapidly, and there is some evidence to suggest that: Large dogs are often diagnosed with age-related diseases sooner than their smaller counterparts. 

But MacLean said he has found no similar pattern in cognitive decline. Instead, the relationship between age and cognitive performance seems similar in all dogs, despite significant differences in how long they typically live. He first noticed this pattern while reviewing surveys completed by dog owners for a 2022 paper he co‑authored.

While there are numerous hormonal pathways that regulate growth, MacLean said IGF-1 is a prime target to study in dogs for several reasons: It is known to drive the remarkable variation in dog body size; previous studies have shown that manipulating IGF-1 can influence aging; and there is evidence linking the hormone to better cognitive health in humans and other animals.

So, is IGF-1 preventing age related decline, rather than driving it?

Now just weeks away from launching his next study, MacLean is recruiting several dozen dogs of various breeds. By working with multiple dogs that are physically similar, he hopes to eliminate size‑related factors that could otherwise complicate interpretation.

"Our hypothesis is that dogs with higher IGF-1 concentrations are going to perform better on our cognitive tasks," MacLean said. "That is because IGF-1, in addition to being involved in the body's growth pathways, also affects the brain. While this hormone may cause some bad outcomes like cancer, it may also influence how neurons repair themselves after an injury or even stimulate neural growth in the brain. There are some intriguing studies that show a relationship between IGF-1 concentrations in humans and the risk of dementia, but we're not sure why."

Working alongside MacLean are U of A colleagues Emily Bray, assistant professor of human-animal interaction, and Gene Alexander, professor of psychology in the College of Science, and collaborators from Arizona State University, Colorado State University and Tufts University. 

The team is looking for the community's help in their research by asking owners of 10- to 13-year-old dogs that weigh between 15 and 25 kilograms (33 to 55 pounds) to participate in the upcoming study. Interested community members can email the Arizona Canine Cognition Center for more information or enroll online.