//Aging thesis

Loyal publication recap

Cover Image for Loyal publication recap

From the start, Loyal has pursued publication in peer-reviewed journals. By publishing our research, we ensure transparency, credibility, and accessibility, enabling others to build upon our work and drive progress in their respective fields. No matter whether our results are positive or negative, we at Loyal are committed to sharing our results.

Below is a summary of all of our scientific publications to date.

How metabolic markers of aging affects frailty and quality of life in dogs (NEW 2025)

Declining metabolic function is a common driver of aging-related disease and mortality in many species. While aging-associated metabolic dysfunction has been investigated rigorously in humans, less is known about this in dogs.

In this cross-sectional study, we examined changes with age in key features of metabolic health in dogs, including insulin and glucose, blood lipids, and common clinical laboratory measures, such as liver enzymes. We also looked for any associations with frailty and quality of life. The study enrolled 451 mature, adult companion dogs of diverse breeds and sizes.

We discovered that increasing insulin with age was associated with greater frailty and poorer quality of life. Glucose, in contrast, typically declines with aging in dogs, and dogs with higher glucose actually had reduced frailty scores.

Increasing ALT and ALP were associated with greater frailty and poorer quality of life. Increases in cholesterol, total free fatty acids, and saturated fats (aka “bad fats”) were also associated with higher frailty scores. Adiponectin, a protective hormone produced by metabolically healthy adipose tissue, was associated with lower frailty scores and better health-related quality of life.

Our findings establish novel associations between deleterious aging-associated metabolic changes and validated measures of clinical well-being in companion dogs. Future research should investigate the causality of these associations to inform therapeutic strategies targeting age-associated changes to frailty and quality of life.

  • 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

High-fat diet as a model of metabolic aging in dogs

Understanding how metabolism changes with age is critical in developing therapies to extend lifespan and healthspan. However, studying these changes with natural aging can be difficult due to the long duration of this process. Therefore, experimental models that mirror the metabolic deterioration associated with aging are needed. One model widely used in laboratory species, including dogs, is the high-fat diet (HFD). Feeding a high-fat diet induces metabolic changes similar to those seen with natural aging but in a much shorter period of time.

In this study, we compared measures of metabolic health in dogs fed a HFD with those on a normal diet. We found that the HFD produced resistance to the activity of insulin in the tissue, elevations in blood lipids, and shifts in the structure and function of body fat that are all changes also seen with normal aging in dogs. These findings help us to better understand how energy metabolism changes with age and they support the relevance of a HFD as a model for metabolic aging.


Assessing the impact of a high-fat diet in dogs

  • McKenzie B, Peloquin M, Tovar A, Graves JL, Ratcliff E, Tucker K, Vo K, Greenwood K, Halioua-Haubold CL, Juarez-Salinas D. Feeding dogs a high-fat diet induces metabolic changes similar to natural aging, including dyslipidemia, hyperinsulinemia, and peripheral insulin resistance. Am J Vet Res. 2024 Apr 15;85(6):ajvr.23.11.0253. doi: 10.2460/ajvr.23.11.0253.

Risk factors for osteoarthritis in companion dogs

OA is an age-related degenerative joint disease that causes affected dogs significant pain and stiffness. OA can make it difficult or even impossible for dogs to go on walks and participate in other normal, everyday activities, drastically compromising their quality of life. Because OA is currently incurable once developed, our analysis focused on actionable features of a dog’s health that might predispose dogs to developing OA.

At a high level, we learned that older age, higher adult body weight, gonadectomy status (whether the dog was spayed or neutered), and younger age at gonadectomy were significantly associated with higher risk of OA. We also saw these effects in a subset of representative breeds.


Risk factors for OA in dogs of different breeds and sizes.

  • Graves, J.L., McKenzie BA., Koch Z., Naka A., Spofford N., Morrison J. (2023) Body weight, gonadectomy, and other risk factors for diagnosis of osteoarthritis in companion dogs, Frontiers. Available at: https://doi.org/10.3389/fvets.2023.1275964

The Healthspan study

Developing valid tools that assess key determinants of canine healthspan such as frailty and health-related quality of life (HRQL) is essential to characterizing and understanding aging in dogs. Additionally, because the companion dog is an excellent translational model for humans, such tools can be applied to evaluate gerotherapeutics and investigate mechanisms underlying longevity in both dogs and humans. In this study, we investigated the use of a clinical questionnaire (Canine Frailty Index; CFI; Banzato et al., 2019) to assess frailty and an owner assessment tool (VetMetrica HRQL) to evaluate HRQL in adult companion dogs.


Association between frailty and age in dogs

  • Chen FL. Ullal TV. Graves Jl. Ratcliff ER. Naka A. McKenzie BA.  Carttar TA. Super KM. Austriaco J. Weber SY. LaCroix-Fralish ML. Vaughn J. Evaluating instruments for assessing healthspan: a multi-center cross-sectional study on health-related quality of life (HRQL) and frailty in the companion dog.  bioRxiv 2022.07.21.500746; doi: https://doi.org/10.1101/2022.07.21.500746

Canine Geriatric Syndrome

Biological aging is the single most important factor leading to disability, disease, and death in senior dogs. Since aging is often viewed as a “natural” and inevitable process, it can be difficult to detect early signs. The lack of tools to detect and measure the harmful impact of aging in individual dogs makes it harder to preserve normal health and function and maintain good quality of life.


7 core components of Canine Geriatric Syndrome

  • McKenzie, BA. Chen, FL. Gruen, ME. Olby, NJ. Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience . Front Vet Sci. 2022;21(9):853743. 10.3389/fvets.2022.853743


Phenotype of aging

This review summarizes what we know about the clinical manifestations of aging in dogs—what happens to their appearance, health, and function as they get old. We start by reviewing the physical impacts of aging, including externally visible changes, such as greying of the haircoat and cloudy eyes. We then consider changes in internal organs, including weakening of the immune system, loss of muscle strength, dental disease, and an increased occurrence of cancers.

Next we look at the behavioral hallmarks of aging in dogs. Our canine companions may become less sociable or more anxious, and eventually some will develop canine cognitive dysfunction, and brain disease very similar in both symptoms and underlying mechanisms to Alzheimer’s disease in humans. Such behavioral changes reduce quality of life for both dogs and their human family, so understanding them and developing tools to prevent them is critical.

Connecting the biological mechanisms of aging to the specific diseases and disabilities that reduce quality of life in geriatric dogs is a necessary step in developing treatments to extend healthspan and lifespan.


Lifespan and healthspan in dogs

  • McKenzie, BA. Lacroix-Fralish, ML. Chen, F. The phenotype of aging in the dog: How aging impacts the health and wellbeing of dogs and their caregivers. J Amer Vet Med Assoc. 2022;260(9):963-970. https://doi.org/10.2460/javma.22.02.0088


Comparative veterinary geroscience

The purpose of this review is to describe key mechanisms of aging at the cellular and molecular level and the manifestations of these in the tissues of the musculoskeletal system, adipose, and the brain. This will highlight knowledge gaps and important targets for future research to extend lifespan and healthspan in dogs and cats.

This review focuses specifically on muscle and bone, adipose tissue (or fat), and the brain because the aging of these tissues has some of the greatest impact on health and physical function. Loss of muscle mass and strength, arthritis, and degenerative brain disease are specific manifestations of the general process of aging that have the most serious consequences for the quality of life of older animals.

The ultimate goal of this review is to summarize what we know now and point out where more research is needed. This will facilitate continued progress in understanding aging and in developing therapies to extend healthy lifespan.


Aging is a web of interacting elements driving disability, disease, and death

  • McKenzie, BA. Comparative Veterinary Geroscience: Mechanism of molecular, cellular, and tissue aging in humans, laboratory animal models, and companion dogs and cats. Amer J Vet Res. 2022;83(6): https://doi.org/10.2460/ajvr.22.02.0027


Assessment and management of declining physical function in aging dogs

Aging is the leading cause of disability, disease, and death in adult dogs. One major consequence of aging is diminishing physical function. In humans, there are validated clinical assessments of physical function that can predict disability, morbidity, and mortality. There are also effective interventions to preserve and restore function and reduce the risk of death and disease in the elderly. This review evaluates the decline in physical function with age in dogs and the potential utility in this species of clinical assessment tools and interventions developed for humans.


Integrative levels of physical function

  • McKenzie BA, Chen FL. Assessment and Management of Declining Physical Function in Aging Dogs. Top Companion Anim Med. 2022 Oct 21;51:100732. doi: 10.1016/j.tcam.2022.100732. Epub ahead of print. PMID: 36273752.