In 2020, the Dog Aging Project began enrolling tens of thousands of companion dogs in the United States in a long-term longitudinal study of normative aging. The goal of the Dog Aging Project is to characterize the range of aging patterns in dogs, to discover the genetic and environmental factors that shape this variation, and to identify the mechanisms by which they do so.
The researchers aim 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.
In a new paper, the team surveyed the plasma metabolome from the first year of sampling of the Precision Cohort of the DAP—a subset of the approximately 50,000 total dogs in the project—recruited specifically for deep molecular profiling. In doing so, it 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.”
This work is published in Aging Cell in the paper, “Protein catabolites as blood-based biomarkers of aging physiology: Findings from the Dog Aging Project.”
“Because dogs age like humans, share our environment, and receive comparable healthcare, they’re an ideal model for studying aging,” said Daniel E.L. Promislow, PhD, senior scientist at Tufts University and co-director of the Dog Aging Project. “Our hope is that blood metabolites like those studied here have the potential to serve as powerful biomarkers for tracking the processes that drive healthy aging, not only in dogs but in humans as well.”
The team analyzed a panel of 133 aqueous metabolites measured in plasma collected from 784 Precision Cohort dogs, representing a diversity of ages during their first year of enrollment in the Cohort. By analyzing metabolites from blood samples, investigators identified effects of age on more than one-third of measured metabolites. They also found that post-translationally modified amino acids, which are generated from protein break-down, are strongly linked with age in dogs. These molecules might be promising indicators of physiological aging. Also, the study pointed to an important role of the kidney in the relationship between age and blood metabolites.
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.
The research identified effects of age on approximately 36% of measured metabolites. It also uncovered a novel biomarker of age in the post-translationally modified amino acids (ptmAAs). The authors note that 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, they note.
