Scientific Results: Protein Catabolites as Blood-Based Biomarkers of Aging Physiology: Findings From the Dog Aging Project

Author

Benjamin R Harrison

Where was it published?

Aging Cell

 What is this paper about?

The Dog Aging Project is working to understand how and why dogs age. By studying genetics, environment, and biology, researchers hope to learn what affects healthy aging in dogs. One area of interest is the identification of aging biomarkers, which are measurements that can be made across the life of a dog that reflect their aging.

In this study, the researchers focus on the plasma metabolome – the hundreds of different small molecules that can be measured in blood samples – which are taken annually from the Precision Cohort of the DAP. Among these molecules, they identified a group called post-translationally modified amino acids (ptmAAs), whose only known source is the breakdown of protein.

By analyzing the samples collected from about 800 dogs of various ages at their entry into the DAP, researchers found that these ptmAAs were generally higher in abundance in older dogs compared to younger dogs. ptmAAs had been measured in several studies of aging biomarkers in humans, however at the time, a connection was not made to protein catabolism.

Tracing the potential physiological causes for the rise in ptmAAs in older dogs, DAP researchers found evidence that kidney function drives much of this pattern. The source of the protein catabolites is not known, and diet did not appear to strongly influence this pattern.  This study, the first one published from the DAP investigation of the blood metabolome, identifies an aging biomarker in dogs and humans and sheds light on a potential physiological driver of this variation.

What do these results mean for me and my dog?

Every dog owner has seen the aging process happen in the many ways their dog changes as they grow older. This study gives us a window into the changes that are impossible to see, those inside the bloodstream.  Thus, your participation is making this research possible. By sharing your dog’s health information and blood samples, you’ve helped scientists discover important clues about how dogs age.

Your dog’s blood tells a story about aging:
Researchers have found that certain molecules in blood increase as dogs get older. By studying these changes, scientists can learn more about how your dog’s body is aging, not just how many years old they are.

Why your participation matters:
By allowing researchers to collect blood and health information from your dog, you are helping to develop tools that could one day predict health problems, improve care, and support longer, healthier lives for dogs.

What’s next:
This is just the first step. As the study continues, researchers will keep following these dogs to learn how these molecules change over time and what they can tell us about aging and disease

Where can I learn more?

Harrison BR, Partida-Aguilar M, Marye A, et al. Protein Catabolites as Blood-Based Biomarkers of Aging Physiology: Findings From the Dog Aging Project. Aging Cell. 2025 Nov;24(11):e70226. doi: 10.1111/acel.70226. Epub 2025 Oct 22. PMID: 41121965; PMCID: PMC12611326.

Abstract

Our understanding of aging has grown through the study of systems biology, including single-cell analysis, proteomics and metabolomics. Studies in lab organisms in controlled environments, while powerful and complex, fall short of capturing the breadth of genetic and environmental variation in nature. Thus, there is now a major effort in geroscience to identify aging biomarkers that might be applied across the diversity of humans and other free-living species. To meet this challenge, the Dog Aging Project (DAP) aims to identify cross-sectional and longitudinal patterns of aging in complex systems, and how these are shaped by the diversity of genetic and environmental variation among companion dogs. Here we surveyed the plasma metabolome from the first year of sampling of the Precision Cohort of the DAP. By incorporating extensive metadata and whole genome sequencing, we overcome the limitations inherent in breed-based estimates of genetic effects, and probe the physiological basis of the age-related metabolome. We identified effects of age on approximately 36% of measured metabolites. We also discovered a novel biomarker of age in the post-translationally modified amino acids (ptmAAs). The ptmAAs, which are generated by protein hydrolysis, covaried both with age and with other biomarkers of amino acid metabolism, and in a way that was robust to diet. Clinical measures of kidney function mediated about half of the age effect on ptmAA levels. This work identifies ptmAAs as robust indicators of age in dogs, and points to kidney function as a physiological mediator of age-associated variation in the plasma metabolome.