//Aging thesis

Can science actually make your dog live longer? The Purina study

Brennen McKenzie, MA, MSc, VMD
by Brennen McKenzie, MA, MSc, VMD
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Disclaimer: Loyal has no affiliation or relationship with Purina. We’re writing about two foundational studies their scientists published in 2002 and 2008 that have informed important research in the longevity field.

One of the first logical questions for a good skeptic to ask when thinking about canine aging biology is whether it is plausible that we can extend lifespan (years lived) and healthspan (healthy years lived) in dogs. Is there reliable evidence that aging is not something immutable and inevitable but something we can actively alter? If so, how strong is that evidence, what does it suggest we should try, and what do we still need to learn?

Longevity research decades old — from worms to mice to dogs

The good news is that there are decades worth of research showing that lifespan can be extended and age-associated disease reduced in a variety of species. Much of this research has involved lab animals, such as roundworms, fruit flies, and mice1-3. Such studies are useful for understanding basic principles in biology, and they suggest hypotheses to test in other species, but they aren’t sufficient to prove a given treatment or preventative intervention will work in other species (such as dogs). There are even some laboratory studies in dogs that strengthen the basic understanding of aging and how we might influence it, but again this only gets us so far. 

Fortunately, we have more than this. While we can’t predict whether specific drugs or many other treatments will work until we’ve done the science to test them, we know that healthspan and lifespan can be extended in dogs because it’s been done! The one method that has been shown effective in many different animals, including dogs, is caloric restriction.

Caloric restriction can increase your dog’s lifespan

Caloric restriction is defined as a substantial reduction in calorie and nutrient intake without malnutrition. The specific details vary among studies, but in general the key appears to be reducing total calorie intake significantly (perhaps 20-40%) without inducing micronutrient (vitamin and mineral) deficiencies. There are some other strategies that have proven effective or appear promising — for example, changes in protein intake or intermittent fasting — but overall the best evidence is for total calorie reduction.

The good news is that there is strong evidence for the benefits of caloric restriction in dogs. One long-term study in Labrador retrievers paired littermates by sex and weight and then randomly assigned one to unrestricted feeding and the other to a calorie intake 25% less than its paired littermate4,5. In order to avoid obesity in the control dogs, at about 3 years of age the protocol was changed so these dogs were fed to maintain an optimal body condition rather than ad libitum (as often as they wanted), but the calorie restricted dogs were still fed 25% less than their paired littermates ate. The study ran for the entire lives of these dogs.

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The calorie restricted dogs had a median lifespan of 13 years, 1.8 years (16%) longer than the 11.2 years in the control group.

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The calorie restricted dogs had a median lifespan of 13 years, 1.8 years (16%) longer than the 11.2 years in the control group. Calorie restricted dogs also developed arthritis 1.5 years later on average than the control dogs. Some dogs developed cancer in both groups, but the average age of death from this cause was 2 years later in the restricted calorie group (11.6 years vs 9.7 years)4,5.

A representation of Fig. 1. Survival curves for calorie restricted (green 一) and control (ー・ー) feeding groups from Kealy et al., J Am Vet Med Assoc 220, 1315-1320, 2002.

Caloric restriction can positively impact your dog’s metabolic health

This study also showed that increasing insulin resistance independently predicted shorter lifespans and more chronic disease. Insulin resistance and chronically elevated blood insulin levels have been identified in other species as a feature of aging-related metabolic dysfunction, and these data suggests that is also true in dogs.

There are several laboratory measures of glucose metabolism and insulin activity in dogs, including insulin sensitivity, insulin AUC (area under the curve — or how much insulin is needed to process glucose in the body), glucose AUC (or how fast glucose appears and how much time is needed for the body to uptake and use up the glucose), and peak insulin.

All of these measures showed impaired glucose metabolism and insulin response in the control dogs compared to those dogs who were calorie restricted.5 (In other words, all these values were significantly worse in the non-calorie restricted dogs.) This suggests that some of the benefits of calorie restriction may stem from preservation of healthy glucose metabolism and insulin response, and that other therapies that achieve this may have similar positive effects.

Taken together, data from this study shows that a decrease in metabolic health is tied to increased morbidity (or the occurrence of disease). This suggests that maintaining insulin sensitivity through dietary management or other interventions could be crucial for extending healthspan and lifespan in dogs.

Values related to metabolic health – insulin and glucose response to intravenous glucose challenge of 9-12 year old control-fed (CF) and calorie restricted (DR) Labrador retriever dogs from Table 3. Lawler et al., Br J Nutr. 2008;99(4):793–805.

Caloric restriction can be difficult to sustain long-term

Dramatic, lifelong caloric restriction is not a practical method of extending lifespan and healthspan in dogs. Without appropriate diet formulation and close monitoring, it is easy to cause malnutrition, which can undermine the potential benefits and even be directly harmful. Feeding is also an important element in the human-animal bond, and asking owners to drastically restrict their dogs’ caloric intake for life can interfere with this bond and the success of the human-dog relationship.

Additionally, obesity is a tremendous and growing problem in companion dogs. It’s hard enough to feed our dogs appropriately to maintain a healthy weight, so choosing to severely restrict their food intake even to obtain significant lifespan and health benefits seems unlikely to be possible for most of us. 

Alternatives to caloric restriction — what Loyal is working towards

Fortunately, there may be alternatives to caloric restriction for improving the lifespan and healthspan of dogs. Studies of caloric restriction have taught us a lot about the fundamental biology of aging, and there are many potential means to achieve some of the benefits of caloric restriction other than feeding dramatically less food to our dogs. Promising avenues of future research may include diets with different composition, the timing of feeding, and medicines that mimic aspects of the physiologic response (and positive effects) of caloric restriction. 

While no clearly effective longevity therapy is yet available, science has already proven that aging can be influenced. There are many different ongoing research efforts aiming to translate the decades of knowledge concerning aging biology into more, healthier years for our dogs — including what we’re working on at Loyal! Science will ultimately tell us which, if any, will work and what the relative risks and benefits will be, as is always the case, but having a plausible hypothesis and established potential mechanisms is a good first step.

Sources

  1. Kenyon, C., Chang, J., Gensch, E. et al. A C. elegans mutant that lives twice as long as wild type. Nature 366, 461–464 (1993). https://doi.org/10.1038/366461a0

  2. Mair W, Goymer P, Pletcher SD, Partridge L. Demography of dietary restriction and death in Drosophila. Science. 2003 Sep 19;301(5640):1731-3. doi: 10.1126/science.1086016. PMID: 14500985.

  3. Mao K, Quipildor GF, Tabrizian T, Novaj A, Guan F, Walters RO, Delahaye F, Hubbard GB, Ikeno Y, Ejima K, Li P, Allison DB, Salimi-Moosavi H, Beltran PJ, Cohen P, Barzilai N, Huffman DM. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat Commun. 2018 Jun 19;9(1):2394. doi: 10.1038/s41467-018-04805-5

  4. Kealy RD, Lawler DF, Ballam JM, Mantz SL, Biery DN, Greeley EH, Lust G, Segre M, Smith GK, Stowe HD. Effects of diet restriction on life span and age-related changes in dogs. J Am Vet Med Assoc. 2002 May 1;220(9):1315-20. doi: 10.2460/javma.2002.220.1315. PMID: 11991408.

  5. Lawler DF, Larson BT, Ballam JM, et al. Diet restriction and ageing in the dog: major observations over two decades. Br J Nutr. 2008;99(4):793–805. doi:10.1017/S0007114507871686