Fight Aging!

For research purposes, dogs are argued to be a good compromise between the very long life span of humans, meaning costly and lengthy studies that result in high quality data, and the very short lives of mice, meaning less expensive, shorter studies, but questions regarding the relevance of the data to human medicine. Mice are not humans, and any number of efforts to produce new medical technologies have been shipwrecked on that rock. Dogs, of course, are also not humans, but they are much closer than mice in terms of aging and its relationship with cellular biochemistry and metabolism. To pick one example from the scientific community, the recently established Dog Aging Project is an ongoing effort to produce useful data on methods of modestly slowing aging, run by one of a number of research groups who think along these lines.

Age is the greatest risk factor not only for the probability of death, but also for the majority of morbidities associated with mortality. However, studies to identify factors that alter patterns of aging using animal models have focused on lifespan and age-specific mortality, rather than the underlying patterns of morbidity that lead to death. This gap is due in part to the difficulty of measuring causes of mortality in the standard animal models in aging studies. For example, age-related morbidity and causes of mortality in the commonly studied models of aging range from the not well understood (and often not studied) in mice, to the poorly understood in flies and worms, to nonexistent in yeast.

In addition, many diseases important to human aging (e.g., cardiovascular disease and dementia) do not develop spontaneously in our commonly studied model organisms. To this end, we need a model organism that allows us to understand not only age-related mortality, but also age-related morbidity and causes of death. The companion dog (i.e., dogs that reside under their owner's care) has the potential to fill this gap and to enable us to better understand the genetic and environmental factors that affect lifespan, and the underlying forces that shape age-specific morbidity and mortality.

Over the last 200 years, individual dog breeds have been highly inbred, with the result that genetic variation is relatively limited within breeds, but considerable among breeds. Thanks in large part to this history of intense breeding for specific morphological and behavioral traits, dogs are the most phenotypically diverse mammalian species on the planet. This diversity is found not only in morphology and behavior, but also in life-history traits, where across breeds, dogs exhibit an almost twofold difference in average longevity and enormous variation in risk of specific diseases.

Dogs also have a sophisticated veterinary healthcare system, second only to that of humans, allowing clinicians to diagnose and treat specific diseases, and to identify exact causes of death. For example, unlike mice, companion dogs experience a diversity of spontaneously occurring diseases similar to those of humans, such as age-related neurologic disease, renal disease, endocrine disease, and also experience obesity and its attendant risks. These phenomena allow researchers not only to study the pathologies that influence mortality, but also to understand different comorbidities and multiple chronic conditions that canines exhibit.

Surprisingly, while we know a great deal about the age-specificity of human morbidity, substantially less is known about the degree to which other species, including dogs, show similar disease-specific patterns of aging. Such comparisons are critical in our efforts to develop powerful models to identify the genetic and environmental determinants of morbidity and mortality. Here, we present a comparative analysis of causes of mortality in both humans and companion dogs. We determine the extent to which the companion dog may provide an excellent model of human aging and the degree to which causes of mortality correlate between the two species. Our results lay the groundwork for future use of the domestic dog as a model of human aging and longevity.

Link: https://doi.org/10.1111/acel.12737