Publication highlight: What lab values tell us about dogs’ frailty and quality of life
Our goal at Loyal is to extend healthy lifespan in dogs, giving people and their dogs more happy time together by developing drugs that directly target the underlying mechanisms of aging. One key element of achieving success in this effort is conducting research that connects the dots between the fundamental biology of aging and the real-world experience of aging dogs.
Earlier this year, we published a peer-reviewed scientific paper reporting the results of one of our clinical studies that does just that: For the first time, we’ve shown a connection between markers of metabolic aging and real-world clinical outcomes in dogs — giving us confidence that addressing metabolic dysfunction, with solutions like LOY-002, is a possible path to extend the healthy lifespan of dogs.
These findings have the potential to shape the way veterinarians approach senior dog care, and they’re also a strong validation of how we approach aging at Loyal.
How did we measure these values?
In 2023, we published the initial findings of our Healthspan study, which tested the Canine Frailty Index (CFI) and Health-related Quality of Life (HRQL) tools in 451 dogs of various breeds and ages.
What’s new? We compared these results to specific blood markers in the samples we collected, which allowed us to see exactly how these individual markers were associated with dogs’ quality of life and frailty at different stages of life.
Why are frailty and quality of life important to lifespan?
Why are frailty and quality of life important to lifespan?
Frailty is a good overall measure of the impact of aging on health and function. Using the CFI, a veterinarian integrates a broad set of factors into a single numerical score that represents how much negative impact aging has had on the health of an individual dog. Some of the changes considered include unexpected weight loss, difficulty standing or climbing stairs, and diagnoses of specific diseases such as diabetes or cancer.
Quality of life impacts dogs’ health and happiness and is one of the main factors that influence an owner’s decision to euthanize their dog in old age. The HRQL is a survey tool for dog owners which summarizes the impact of changes in health on a dog’s overall quality of life.
Which lab values correspond with clinical outcomes?
These markers of metabolic aging are associated with quality of life and frailty.
The indicators of metabolic health we evaluated included insulin, adiponectin, and various important fats that circulate in the blood, including cholesterol and saturated fats. As expected, we were able to confirm that metabolic health declines with age in dogs. Insulin was higher and adiponectin was lower. Just as in humans, cholesterol and other blood lipids also increased with age.
The most significant finding was that many of these markers of metabolic dysfunction are associated with CFI and HRQL scores. This is the first time these values have been linked to these measures of healthspan, which gives us confidence that by addressing metabolic dysfunction, we'll be able to help dogs age healthier and live longer.
As we discussed previously, insulin increases with aging, increasing the risk of age-associated diseases, such as cancer. Adiponectin is an essential, protective hormone that regulates metabolic function and combats the harmful effects of high insulin. Both have proven to be important drivers in how well a dog ages.
The most significant finding was that many of these markers of metabolic dysfunction are associated with CFI and HRQL scores. This is the first time these values have been linked to these measures of healthspan, which gives us confidence that by addressing metabolic dysfunction, we'll be able to help dogs age healthier and live longer.
A full breakdown of the data
A full breakdown of the data
Changes in markers of metabolic dysfunction with age in dogs
The importance of markers of metabolic dysfunction isn’t always appreciated in veterinary medicine. However, these age-associated metabolic changes happen in both species, and they lead to many similar health problems, such as an increase in the risk of cancer and other age-associated diseases.
Insulin and adiponectin are associated with increasing frailty and declining quality of life.
Changes in the metabolic activity of adipose tissue (fat) is also a typical feature of metabolic aging and is associated with decreases in the hormone adiponectin, which protects metabolic health. Decreasing adiponectin in humans is associated with a higher risk of disease and a shorter lifespan.
Increasing frailty and decreasing quality of life scores were associated with increases in insulin and with decreasing levels of adiponectin, fitting with the understanding that metabolic dysfunction causes at least some of the change in health and quality of life seen with aging. A study like this cannot definitively prove that there is such a causal relationship, but it is supportive of that explanation. 
Cholesterol and some fatty acids were associated with worsening frailty scores
Dyslipidemia, or unhealthy changes in the amount of some fats, like cholesterol and specific fatty acids in the blood, have been associated with the health effects of aging and shorter lifespan in humans and rodents. Our study is the first to show that this is associated with worsening frailty scores, a specific measure of healthspan.
Other values we looked at: liver enzymes
Finally, we evaluated some common clinical chemistry tests often run as part of routine bloodwork in senior dogs. The most consistent were a couple of liver enzymes, ALT and ALP. These are often elevated in older dogs, and if the changes are small, vets often assume they represent “normal aging” and aren’t a problem.
However, in our study, even though all ALT and ALP values remained within the normal reference range, increases in these enzymes were associated with worsening frailty and quality of life as measured by the CFI and the HRQL.
Because these values are already routinely measured, they could be very useful indicators of metabolic status in older dogs and could inform how vets approach treatment one day.
What’s next for Loyal’s research?
In addition to the findings published in this recent paper, we are doing additional studies in the healthspan dogs and in the lab. In one of these, we have duplicated some of the findings from this study, confirming that insulin increases and adiponectin decreases in older dogs. We have also found that there are changes in the number and types of white blood cells similar to those seen in elderly humans, and these are likely related to the declining effectiveness of the immune system with age.
Other factors, such as red blood cell counts, also change in older dogs in ways similar to humans. However, some of the changes we have seen, such as increases in platelets (needed for blood clotting) are in the opposite direction usually seen in humans. This research is helping to refine our understanding of how dogs and people are both the same and different in the ways they age.
→ To read the full study, access the publication in Scientific Reports.
Learn more about lab values as hidden signs of aging in our 1.0 CE course →
For vets, here’s a version of the Canine Frailty Index for your clinic →
Sources
McKenzie, B., Peloquin, M., Graves, J.L. et al. Changes in insulin, adiponectin and lipid concentrations with age are associated with frailty and reduced quality of life in dogs. Sci Rep 15, 5380 (2025). https://doi.org/10.1038/s41598-025-89923-z
Chen, F.L., Ullal, T.V., Graves, J.L. et al. Evaluating instruments for assessing healthspan: a multi-center cross-sectional study on health-related quality of life (HRQL) and frailty in the companion dog. GeroScience 45, 2089–2108 (2023). https://doi.org/10.1007/s11357-023-00744-2
McMahon, J.E., Graves, J.L., Tovar, A.P. et al. Translational immune and metabolic markers of aging in dogs. Sci Rep 15, 14460 (2025). https://doi.org/10.1038/s41598-025-99349-2