As noted here recently, model organisms are essential to biogerontology: given the evolutionary conservation of aging-related pathways, we should be able to learn about human aging by studying animals with shorter lifespan. Models can be assessed in a variety of ways, often in terms of ease of use (e.g., being genetically tractable or having a short lifespan) or how closely they resemble humans (e.g., in terms of genetic relatedness or similarity of life history).
Unfortunately, there tends to be a tradeoff between those two features: the easiest animals to work with in the laboratory are the most different from humans. Miceare unquestionably important models: their 2–3-year lifespan makes them ideal for longevity studies, and they are very similar to humans in particular biochemical and cell-biological ways. However, the spectrum of age-related disease in mouse differs from that of humans (among other things, wild-type mice don’t really develop cardiovascular disease or dementia), and the environments in which they live differ as well.
This raises serious challenges to the model organism dogma that if an anti-aging intervention works in mice, it will probably work in humans: Aging pathways are conserved between the two species, but specific aspects of the aging process differ dramatically.
As an alternative, some have proposed the companion dog, a model that would sacrifice some ease of use in exchange for a closer approximation of human aging. Dogs are indeed longer-lived than rodents, with lifespans just under an order of magnitude longer than those of mice, and a similar amount shorter than ours. Furthermore, they share our environment, literally living in our homes with us and (whether or not they’re supposed to) eating the same food.
But is the aging process in dogs really similar to that in humans? A recent study answers in the affirmative, providing key support for the idea that dogs could be used to understand normal aging in humans and test anti-aging medicines.
The authors used data from more than 100,000 people and nearly as many dogs in the US and UK to compare the patterns of age-related mortality and morbidity (here meaning “the rate of disease”) between the two species. They found extensive similarities: the survival curves are very similar (when normalized against maximum lifespan), as is the incidence of chronic conditions arising with advanced age. The rank order of causes of death are also strongly correlated (subject to a qualification that we’ll address below), the proportion of individuals dying of cancer at each normalized age is comparable, and—when we exclude lifestyle-related diseases (e.g., lung cancer caused by smoking) —the same organ systems are involved.
The major difference between dogs and humans is that we get far more cardiovascular diseases than our best friends, which is somewhat surprising given that we think of CVD as a lifestyle-related disease, and dogs and humans share both environmental influences and to some extent lifestyle (e.g., fun fact: obese people are likelier to have obese dogs). The authors argue that this is still informative, as it implies that the difference in CVD incidence is genetically determined, allowing us to learn about CVD pathogenesis in humans by investigating the differences between the cardiovascular systems of canines and primates.
Nonetheless, the similarities are striking, providing important evidence that dogs could serve as both a fundamental model (i.e., to learn about the molecular details of aging) and a translational model (i.e., to test interventions on a shorter timeframe than would be possible in humans). Some of this work is already underway, and I direct interested readers to the Dog Aging Project for the details of longitudinal lifespan studies and even an intervention study involving rapamycin. (The DAP is one of my favorite things in biogerontology, but rather than shortchange it by trying to summarize here, I’ll devote a full post or two to the project at a later time.)
The benefits of helping dogs live longer are manifold—not only will it help us test medications that could someday be used to extend healthspan in humans, it will enable us to keep our beloved companions around for longer, enriching our own lives in the countless ways that they do. As anyone who has ever loved a dog knows, this is an end in itself.
Hoffman et al. “The companion dog as a model for human aging and mortality.” Aging Cell 19 Feb 2018. DOI:10.1111/acel.12737