Through the NIA-supported Dog Aging Project (DAP), scientists aim to understand how a complex combination of genes, lifestyle, and environment influence aging not only for dogs but for humans as well. In a perspective recently published in Nature, the researchers describe how they hope to establish the foundation for an innovative, community science approach to aging research in dogs.
There is still much to learn about the mechanisms underlying individual aging. Most of what is known about the biology of aging comes from laboratory studies of mammals such as mice and rats, and invertebrates like fruit flies and nematodes. To better understand how genes and environment affect aging in animals outside of a lab and closer to our own life-course experiences, and to generate knowledge that could more readily translate to human aging, the DAP has turned to the companion dog.
The companion dog is an ideal animal to study biological aging. Dogs are one of the most variable animal species in terms of size, shape, and behavior. Like humans, dogs vary in life expectancy and the spectrum of diseases they are likely to encounter. Companion dogs experience nearly every functional decline and disease of aging that people do, and these diseases are diagnosed and treated within a health care system that parallels human health care in many ways. Dogs also share the human environment, and given that they age more rapidly than humans, they enable unique opportunities for longitudinal and interventional studies.
DAP-targeted study populations consist of dogs of all breeds (purebred and mixed breed), ages, sizes, and sexes. Participation in the DAP is open to all geographic regions in the United States, including urban, suburban, and rural areas. DAP scientists are collecting a wide range of information — electronic veterinary medical records, environmental data, and genome-wide sequencing — as well as blood, urine, hair, and feces.
The key outcomes expected include:
- Data that will provide veterinarians and scientists with tools to assess how well a specific dog is aging and set the stage for studies on factors that influence normal aging. DAP researchers have already begun collecting and analyzing the data that lay the groundwork for canine-specific aging processes.
- Whole-genome sequencing data that will help identify genetic variants, environmental and lifestyle factors, and the interactions that are associated with diverse measures of aging. The DAP is on track to complete sequencing of the genomes of 10,000 dogs by the end of 2022.
- The creation of a systems biology model of aging in dogs through the annual measurement of the animals’ physiological status — from the whole organism via physical measurements, to the molecular level through the collection and analysis of biological specimens. These data will generate predictive and prognostic biomarkers of aging and will point to causal factors that explain the mechanisms by which specific genetic or environmental factors influence aging. These should also be useful biomarkers for clinical studies to develop anti-aging therapies.
The DAP also includes a clinical trial in dogs using a one-year course of weekly low-dose rapamycin, which has been shown to extend lifespan and improve health in mice. The intent is to test the hypothesis that this compound can increase lifespan, improve heart and cognitive function, and reduce age-related disease incidence in middle-aged, large-breed dogs. This represents the first clinical trial of a drug with lifespan and healthspan metrics as endpoints in any species outside of a laboratory.
In addition to making important contributions to veterinary medicine, the ambitious goals set by the DAP research initiative hold the potential of transforming the field of aging research. Like other longitudinal studies, the success of the DAP depends on strong and enduring relationships with many stakeholders, including participating dog owners, veterinarians, and researchers. DAP researchers continue to devote considerable effort to participant retention and capturing the diversity of U.S. dog owners that is yet to be fully represented in the study population. Through these efforts, they aim to establish the foundation for an innovative, community science approach to aging research in dogs. Dog owners interested in participating are encouraged to nominate their dog at dogagingproject.org.
This research was supported by NIA grant U19AG057377.
References: Creevy KE, et al. An open science study of ageing in companion dogs. Nature. 2022;602, 51–57. doi:10.1038/s41586-021-04282-9