The Dog Aging Project: Genetic and Environmental Determinants of Healthy Aging in Companion Dogs

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Project Summary Age is the single greatest risk factor for many diseases in humans, including most major causes of mortality. Studies in short-lived model organisms in the laboratory environment have revealed conserved molecular pathways associated with aging. However, we do not know to what extent these discoveries explain the considerable variation in rates of aging observed in natural populations, including humans. Large-scale human studies can teach us a great deal about determinants of aging, but they are costly and can take decades. We need a translationally relevant model that can help us understand the genetic and environmental factors that shape aging in the natural world, that can reveal the mechanisms underlying these relationships, and that is suitable for testing interventions that we might consider in human populations. To address this unmet need, we created the Dog Aging Project, a long-term longitudinal study of healthy aging in the companion dog, Canis lupus familiaris. The dog is an ideal model. They vary tremendously not only in size, shape, and behavior, but also in life expectancy and age-related risk of disease. Dogs share our disease burden as well as our environment, and have a sophisticated health care system to diagnose, treat and prevent diseases. Given their relatively short lifespan, we can learn from dogs what would take decades in humans. The Dog Aging Project began in 2018, creating a highly collaborative team with the breadth of experience needed to build this game- changing study. Our team has built a powerful infrastructure to recruit thousands of participating dog-owner pairs, and to collect owner-reported survey data, publicly available environmental data, and biospecimens for whole genome sequencing, clinical chemistry, and -omic measures. To date, we have enrolled over 44,000 dogs into this long-term study, far surpassing our original goal. Dog Aging Project data and biospecimens are not only being studied by researchers on the Dog Aging Project, but are also being accessed by interested researchers outside of the team, fulfilling the promise of the Dog Aging Project as an Open Science resource. The Dog Aging Project has made excellent progress towards the overarching goals of this U19, which are 1) to define aging in dogs through novel indices of frailty, multimorbidity and inflammaging; 2) to explain aging in dogs by discovering the genetic and environmental factors that influence aging, and by identifying intermediate molecular traits—metabolome, microbiome, and epigenome—through which this influence unfolds; and 3) to intervene in aging, in the first double-blind, placebo-controlled veterinary clinical trial to assess the effects of a promising drug, rapamycin, on lifespan and healthspan in companion dogs. Our excellent progress has been made possible by the five Cores and four Projects that collaborate in a way that ensures the whole of the Dog Aging Project is far greater than the sum of its parts. The Dog Aging Project will have a major impact on geroscience and veterinary science, and will engage the support of the general public such that the entire field benefits.