The companion dog as a model for human aging and mortality

Abstract

SummaryAround the world, human populations have experienced large increases in average lifespan over the last 150 years, and while individuals are living longer, they are spending more years of life with multiple chronic morbidities. Researchers have used numerous laboratory animal models to understand the biological and environmental factors that influence aging, morbidity, and longevity. However, the most commonly studied animal species, laboratory mice and rats, do not experience environmental conditions similar to those to which humans are exposed, nor do we often diagnose them with many of the naturally occurring pathologies seen in humans. Recently, the companion dog has been proposed as a powerful model to better understand the genetic and environmental determinants of morbidity and mortality in humans. However, it is not known to what extent the age‐related dynamics of morbidity, comorbidity, and mortality are shared between humans and dogs. Here, we present the first large‐scale comparison of human and canine patterns of age‐specific morbidity and mortality. We find that many chronic conditions that commonly occur in human populations (obesity, arthritis, hypothyroidism, and diabetes), and which are associated with comorbidities, are also associated with similarly high levels of comorbidity in companion dogs. We also find significant similarities in the effect of age on disease risk in humans and dogs, with neoplastic, congenital, and metabolic causes of death showing similar age trajectories between the two species. Overall, our study suggests that the companion dog may be an ideal translational model to study the many complex facets of human morbidity and mortality.

Megaloneurite, a giant neurite of vasoactive intestinal peptide and nitric oxide synthase in the aged dog and identification by human sacral spinal cord

“…Aging animal model should be more important for urogenital dysfunction. In general, dog is suggested to be suitable animal model for aging research [36,37]. These previous dog model of urogenital dysfunction should be considered with aging study in future [110,111].…”

“…For human conditions and diseases, the dog recently is considered as a natural model and experimental observation of the canine aging phenotype could be concluded relating that of the human [36]. The companion dog may be used as an experimental model to study of human morbidity and mortality" [37]. However, study of VIP and NOS positivity in the aged dog is still needed to confirm in the aged dog.…”

Spontaneous dog osteoarthritis — a One Medicine vision

“…Dogs typically live into old age, come in a variety of shapes and sizes (from highly athletic to sedentary and overweight) and live in close proximity to humans. As dogs develop many age-related chronic diseases and comorbidities on a foreshortened timescale (breed-influenced life expectancy is ~8-12 years) that are analogous to those in humans, there is a growing view that developing our understanding and treatment of dog osteoarthritis (oA) could lead to breakthroughs in human oA 153 .…”

“…Currently, cancer research is the field that has most readily adopted and successfully applied a One Medicine approach. Cancers account for >25% of dog mortalities 153 and, like OA, the multifactorial and complex aetiology of cancer reduces the predictive value of rodent models. The Canine Comparative Oncology Genomics Consortium initiated an extensive, naturally occurring canine cancer tissue bio-repository.…”

A Preliminary Study to Investigate the Genetic Background of Longevity Based on Whole-Genome Sequence Data of Two Methuselah Dogs

“…The genetics of aging and longevity has been studied in multiple species, including C. elegans (e.g., Gems and Riddle, 2000), fruit fly (e.g., Lehtovaara et al, 2013), mice (e.g., Piper et al, 2008), dogs (see Hoffman et al, 2018 for a summary), and humans (e.g., Herskind et al, 1996). Based on these studies, longevity is known to be influenced by both genetic and environmental factors (López-Otín et al, 2013), with an estimated heritability of 15-30% in humans (e.g., Herskind et al, 1996); in a comparative study, Yanai et al (2017) synthesized the results currently available on longevity-associated genes (LAGs) from yeast, C. elegans, fruit fly and mouse and studied their orthologs in more than 200 species.…”