Celine Halioua

Four years ago I founded Loyal with a simple vision — to bring to market the first drug explicitly approved and labeled for healthy lifespan extension. Loyal was only a few months old and about five people when we decided to begin by targeting the abnormally short lifespan of large breed dogs with a drug program we code-named LOY-001. 

 what we believe to be the FDA’s first-ever formal acceptance that a drug can be developed and approved to extend lifespan. 

In regulatory parlance, we have completed the technical effectiveness portion of our conditional approval application for LOY-001’s use in large dog lifespan extension. 

As there was no established regulatory path for a lifespan extension drug, we had to design from scratch a scientifically strong and logistically feasible way to demonstrate efficacy of an aging drug. This process took more than four years, resulting in the 2,300+ page technical section now approved by the FDA. It included interventional studies of LOY-001 in an FDA-accepted model of canine aging and an observational (no-drug) study of 451 dogs.

Our interventional studies with LOY-001 showed that the drug improved clinically-relevant aging parameters. We assessed these in laboratory studies using a dog model that represents accelerated aging. We then correlated those results with quality of life scores in the observational study, as independently measured by dog owners, and health outcomes as measured by veterinarians. This was key to show that the biological benefits of the drug are linked to clinically relevant outcomes.

From our data, the FDA believes LOY-001 is likely to be effective for large dog lifespan extension in the real world. Once we satisfactorily complete safety and manufacturing sections and other requirements, vets will be able to prescribe LOY-001 to extend the lifespan of large dogs while we complete the confirmatory pivotal lifespan extension study in parallel.

If you have a large- or giant-breed dog you may be familiar with the sad reality that these large dogs tend to live shorter lives than smaller dogs — often by half.

Giant breeds like Great Danes have an average lifespan of 7-10 years, while tiny breeds like the Chihuahua live 14-16 years. (source: AKC, O’Neill et al 2013). Not only do they have varying lifespans, but it’s possible that aging and age-associated disease progresses differently among different breeds.

This is unusual — very few if any other animals have such an extreme lifespan variation 

 the same species. Generally, the larger a mammal is, the longer its expected lifespan — a mouse may live two to three years, while elephants can live over 60 years. 

Part of this lifespan disparity comes from the process of selective breeding that “created” these dog breeds.  Historical selective breeding is understood to have created genetic issues like hip dysplasia in German Shepherds and breathing issues in brachycephalic dogs. In large- and giant-breed dogs, breeding for size caused these dogs to have highly elevated levels of IGF-1, a hormone that drives cell growth. High IGF-1 effectively drives these dogs to grow large when they’re young, but high IGF-1 levels in adult dogs are believed to accelerate their aging and reduce their healthy lifespan.

LOY-001 extends lifespan in part by reducing IGF-1 to levels seen in smaller-breed dogs. The IGF-1 axis is one of the most well-studied longevity pathways. In model organisms from 

to mice, reducing IGF-1 extends healthy lifespan, and increasing IGF-1 shortens healthy lifespan. In humans, certain centenarians have been shown to have genetically lower levels of IGF-1.

The breakthrough moment for Loyal was connecting the biological mechanism of big dogs’ size to their short lifespan, and recognizing the big-dog-short-lifespan phenotype may not be inherent, but instead a type of “accelerated aging disorder”.

We designed LOY–001 as a long-acting injectable administered by your veterinarian every three to six months. In parallel, through our 

 partnership with Crinetics, we’re also developing LOY-003, a daily pill to address this same IGF-1 over-expression. 

A regulatory process that ensures safety and effectiveness

Our product strategy has always been centered on earning FDA approval. While more challenging, time intensive, and expensive, I believe achieving FDA approval is critical to demonstrating the scientific legitimacy of lifespan extension drugs.

Most people know that the FDA has a rigorous system for ensuring that pharmaceutical products are safe and effective for humans. The same is true for veterinary medications — the drugs your vet prescribes to your dog, like the Rimadyl my senior Rottweiler takes for her arthritis, have been tested extensively and are regularly monitored by the FDA Center for Veterinary Medicine.

To obtain approval to sell the drug, companies must present extensive data to the FDA in three core areas:

The health and safety of dogs is our top priority in all things, and there’s no higher bar in the United States than the FDA. 

Conditional approval helps us help dogs sooner

The FDA’s expanded conditional approval process allows companies to bring certain products to patients while conducting longer effectiveness studies, specifically when the product meets an important unmet need. This helps us get treatment as early as possible to older dogs who need it most.

To receive conditional approval, the product must meet the same rigorous safety and manufacturing standards as drugs that are fully approved. To stay on the market beyond the five-year conditional approval period, we must demonstrate full efficacy — in our case lifespan extension — in a pivotal study. 

Each milestone we’ve achieved in this methodical, evidence-based process has demonstrated steady progress toward our vision of helping dogs live longer and stay healthy as they age.

This one is especially important because it marks a key step toward FDA approval based on credible, carefully reviewed data.

This process will make it possible for us to bring our products into veterinary clinics everywhere, and lead the charge on a new approach to age-related disease and decline.

That will ultimately mean more healthy years for the dogs we love — and that’s why we’re here.

Thank you so much to the Loyal team for your intelligence, creativity, and determination to reach today’s milestone. Current and former team members who directly contributed to this milestone include: Alex Naka, Ashley Tovar, Ben Parsons, Brennen McKenzie, Dina Juarez-Salinas, Divya Shiroor, Elena Silva, Ellen Ratcliff, Entonio Marietti, Erin McCandless, Frances Chen, Jess Graves, Jessica Austriaco, Jessie George, Julie Vaughn, Kaitlyn Super, Karen Greenwood, Katya Tucker, Matt Peloquin, Michael LaCroix-Fralish, Michelle Nelson, Phil Frankino, Tennery Carttar, and Tyler McQuade. 

Thank you to our earliest investors and advisors, including but not limited to Dave Petrick, Greg Rosen, Josh Kopelman, Laura Deming, Linda Rhodes, and Taylor Greene, who believed in this crazy vision long before it was rational or sensible to do so. 

Here’s what the press is saying this morning:

Could a Drug Give Your Pet More Dog Years?

A Life-Extension Drug for Big Dogs Is Getting Closer to Reality

An anti-aging drug for dogs promises to win owners more time with old pets. It could be FDA-approved soon.

The Secrets of Anti-Aging, Gleaned From Your Dog

S.F. startup that wants to help dogs live longer just got FDA backing

Life-Extending Drug For Big Dogs Moves One Step Closer To FDA Approval

Extending dog years: New drug to increase lifespan of dogs, company awaiting FDA approval

FDA Center for Veterinary Medicine agrees Loyal’s data supports reasonable expectation of effectiveness for large dog lifespan extension

Four years ago I founded Loyal with a simple vision — to bring to market the first drug explicitly approved and labeled for healthy lifespan extension. Loyal was only a few months old and about five people when we decided to begin by targeting the abnormally short lifespan of large breed dogs with a drug program we code-named LOY-001.&nbsp;



Today, I’m so proud to announce that <a href="https://www.businesswire.com/news/home/20231127326868/en/FDA-Agrees-Loyal-Data-Supports-Reasonable-Expectation-of-Effectiveness-for-Large-Dog-Lifespan-Extension">Loyal has earned</a> what we believe to be the FDA’s first-ever formal acceptance that a drug can be developed and approved to extend lifespan. In regulatory parlance, we have completed the technical effectiveness portion of our conditional approval application for LOY-001’s use in large dog lifespan extension.&nbsp;



As there was no established regulatory path for a lifespan extension drug, we had to design from scratch a scientifically strong and logistically feasible way to demonstrate efficacy of an aging drug. This process took more than four years, resulting in the 2,300+ page technical section now approved by the FDA. It included interventional studies of LOY-001 in an FDA-accepted model of canine aging and an observational (no-drug) study of 451 dogs.



Our interventional studies with LOY-001 showed that the drug improved clinically-relevant aging parameters. We assessed these in laboratory studies using a dog model that represents accelerated aging. We then correlated those results with quality of life scores in the observational study, as independently measured by dog owners, and health outcomes as measured by veterinarians. This was key to show that the biological benefits of the drug are linked to clinically relevant outcomes.



From our data, the FDA believes LOY-001 is likely to be effective for large dog lifespan extension in the real world. Once we satisfactorily complete safety and manufacturing sections and other requirements, vets will be able to prescribe LOY-001 to extend the lifespan of large dogs while we complete the confirmatory pivotal lifespan extension study in parallel.







<h2 class="wp-block-heading">What this means for large-breed dogs</h2>



If you have a large- or giant-breed dog you may be familiar with the sad reality that these large dogs tend to live shorter lives than smaller dogs — often by half.



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="576" src="https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dog-small-dog-great-dane-chihuahua-average-lifespan-aging-1-1024x576.jpg" alt="Giant breeds like Great Danes have an average lifespan of 7-10 years, while tiny breeds like the Chihuahua live 14-16 years. (source: AKC, O’Neill et al 2013). Not only do they have varying lifespans, but it’s possible that aging and age-associated disease progresses differently among different breeds.
" class="wp-image-924" srcset="https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dog-small-dog-great-dane-chihuahua-average-lifespan-aging-1-1024x576.jpg 1024w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dog-small-dog-great-dane-chihuahua-average-lifespan-aging-1-300x169.jpg 300w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dog-small-dog-great-dane-chihuahua-average-lifespan-aging-1-768x432.jpg 768w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dog-small-dog-great-dane-chihuahua-average-lifespan-aging-1-1536x864.jpg 1536w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dog-small-dog-great-dane-chihuahua-average-lifespan-aging-1.jpg 1999w" sizes="(max-width: 1024px) 100vw, 1024px" /><figcaption class="wp-element-caption">Giant breeds like Great Danes have an average lifespan of 7-10 years, while tiny breeds like the Chihuahua live 14-16 years. (source: AKC, O’Neill et al 2013). Not only do they have varying lifespans, but it’s possible that aging and age-associated disease progresses differently among different breeds.</figcaption></figure>



This is unusual — very few if any other animals have such an extreme lifespan variation within the same species. Generally, the larger a mammal is, the longer its expected lifespan — a mouse may live two to three years, while elephants can live over 60 years.&nbsp;



Part of this lifespan disparity comes from the process of selective breeding that “created” these dog breeds.&nbsp; Historical selective breeding is understood to have created genetic issues like hip dysplasia in German Shepherds and breathing issues in brachycephalic dogs. In large- and giant-breed dogs, breeding for size caused these dogs to have highly elevated levels of IGF-1, a hormone that drives cell growth. High IGF-1 effectively drives these dogs to grow large when they’re young, but high IGF-1 levels in adult dogs are believed to accelerate their aging and reduce their healthy lifespan.



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="576" src="https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dogs-IGF-1-eigenmann-et-al-1984-Maxwell-et-al-1998-1024x576.jpg" alt="" class="wp-image-927" srcset="https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dogs-IGF-1-eigenmann-et-al-1984-Maxwell-et-al-1998-1024x576.jpg 1024w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dogs-IGF-1-eigenmann-et-al-1984-Maxwell-et-al-1998-300x169.jpg 300w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dogs-IGF-1-eigenmann-et-al-1984-Maxwell-et-al-1998-768x432.jpg 768w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dogs-IGF-1-eigenmann-et-al-1984-Maxwell-et-al-1998-1536x864.jpg 1536w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2023/11/large-dogs-IGF-1-eigenmann-et-al-1984-Maxwell-et-al-1998.jpg 1999w" sizes="(max-width: 1024px) 100vw, 1024px" /></figure>



LOY-001 extends lifespan in part by reducing IGF-1 to levels seen in smaller-breed dogs. The IGF-1 axis is one of the most well-studied longevity pathways. In model organisms from C. elegans to mice, reducing IGF-1 extends healthy lifespan, and increasing IGF-1 shortens healthy lifespan. In humans, certain centenarians have been shown to have genetically lower levels of IGF-1.



The breakthrough moment for Loyal was connecting the biological mechanism of big dogs’ size to their short lifespan, and recognizing the big-dog-short-lifespan phenotype may not be inherent, but instead a type of “accelerated aging disorder”.



We designed LOY–001 as a long-acting injectable administered by your veterinarian every three to six months. In parallel, through our <a href="https://loyalfordogs.com/posts/announcing-our-partnership-with-crinetics-pharmaceuticals">recently-announced</a> partnership with Crinetics, we’re also developing LOY-003, a daily pill to address this same IGF-1 over-expression.&nbsp;







<h2 class="wp-block-heading">A regulatory process that ensures safety and effectiveness</h2>



Our product strategy has always been centered on earning FDA approval. While more challenging, time intensive, and expensive, I believe achieving FDA approval is critical to demonstrating the scientific legitimacy of lifespan extension drugs.



Most people know that the FDA has a rigorous system for ensuring that pharmaceutical products are safe and effective for humans. The same is true for veterinary medications — the drugs your vet prescribes to your dog, like the Rimadyl my senior Rottweiler takes for her arthritis, have been tested extensively and are regularly monitored by the FDA Center for Veterinary Medicine.



To obtain approval to sell the drug, companies must present extensive data to the FDA in three core areas:



<ol class="wp-block-list">
<li>Efficacy — It does what it says it will do; in our case, it extends the lifespan of dogs.</li>



<li>Safety — It’s proven safe for dogs, and any side effects are well-understood and documented.</li>



<li>Manufacturing — We can manufacture it at a consistently high quality, at scale.</li>
</ol>



The health and safety of dogs is our top priority in all things, and there’s no higher bar in the United States than the FDA.&nbsp;



<h2 class="wp-block-heading">Conditional approval helps us help dogs sooner</h2>



The FDA’s expanded conditional approval process allows companies to bring certain products to patients while conducting longer effectiveness studies, specifically when the product meets an important unmet need. This helps us get treatment as early as possible to older dogs who need it most.



To receive conditional approval, the product must meet the same rigorous safety and manufacturing standards as drugs that are fully approved. To stay on the market beyond the five-year conditional approval period, we must demonstrate full efficacy — in our case lifespan extension — in a pivotal study.&nbsp;



<h2 class="wp-block-heading">What this means for all dogs</h2>



Each milestone we’ve achieved in this methodical, evidence-based process has demonstrated steady progress toward our vision of helping dogs live longer and stay healthy as they age.



This one is especially important because it marks a key step toward FDA approval based on credible, carefully reviewed data.



This process will make it possible for us to bring our products into veterinary clinics everywhere, and lead the charge on a new approach to age-related disease and decline.



That will ultimately mean more healthy years for the dogs we love — and that’s why we’re here.



——————



Thank you so much to the Loyal team for your intelligence, creativity, and determination to reach today’s milestone. Current and former team members who directly contributed to this milestone include: Alex Naka, Ashley Tovar, Ben Parsons, Brennen McKenzie, Dina Juarez-Salinas, Divya Shiroor, Elena Silva, Ellen Ratcliff, Entonio Marietti, Erin McCandless, Frances Chen, Jess Graves, Jessica Austriaco, Jessie George, Julie Vaughn, Kaitlyn Super, Karen Greenwood, Katya Tucker, Matt Peloquin, Michael LaCroix-Fralish, Michelle Nelson, Phil Frankino, Tennery Carttar, and Tyler McQuade.&nbsp;



Thank you to our earliest investors and advisors, including but not limited to Dave Petrick, Greg Rosen, Josh Kopelman, Laura Deming, Linda Rhodes, and Taylor Greene, who believed in this crazy vision long before it was rational or sensible to do so.&nbsp;



——————



Here&#8217;s what the press is saying this morning:



New York Times <span style="font-size: 11pt; font-family: Inter, sans-serif; background-color: transparent; font-variant-numeric: normal; font-variant-east-asian: normal; font-variant-alternates: normal; font-variant-position: normal; vertical-align: baseline;">— <a href="https://www.nytimes.com/2023/11/28/science/longevity-drugs-dogs.html" target="_blank" rel="noreferrer noopener">Could a Drug Give Your Pet More Dog Years?</a>



WIRED — <a href="https://www.wired.com/story/a-life-extension-drug-for-big-dogs-is-getting-closer-to-reality/" target="_blank" rel="noreferrer noopener">A Life-Extension Drug for Big Dogs Is Getting Closer to Reality</a>



Business Insider — <a href="https://www.businessinsider.com/longevity-drug-for-dogs-moves-closer-to-fda-approval-loyal-2023-11?r=US&amp;IR=T" target="_blank" rel="noreferrer noopener">An anti-aging drug for dogs promises to win owners more time with old pets. It could be FDA-approved soon.</a>



The Wall Street Journal — <a href="https://www.wsj.com/health/wellness/dog-longevity-anti-aging-loyal-a1f39cb2?reflink=integratedwebview_share">The Secrets of Anti-Aging, Gleaned From Your Dog</a>



San Francisco Chronicle — <a href="https://www.sfchronicle.com/sf/article/s-f-startup-wants-help-dogs-live-longer-got-fda-18522309.php" target="_blank" rel="noreferrer noopener">S.F. startup that wants to help dogs live longer just got FDA backing</a>



IFLScience — <a href="https://www.iflscience.com/life-extending-drug-for-big-dogs-moves-one-step-closer-to-fda-approval-71772">Life-Extending Drug For Big Dogs Moves One Step Closer To FDA Approval</a>



USA Today — <a href="https://www.usatoday.com/story/news/nation/2023/11/30/dogs-drug-lifespan-extended-fda-biotech-company-loyal/71751432007/" target="_blank" rel="noreferrer noopener">Extending dog years: New drug to increase lifespan of dogs, company awaiting FDA approval</a>

Brennen McKenzie, MA, MSc, VMD

From an evolutionary perspective, it isn’t immediately obvious why animals should experience degeneration and illness as they age. Shouldn’t natural selection favor those who are healthier and live longer? Shouldn’t we eventually evolve to live forever since immortal individuals are clearly more “fit” than those who age? 

But evolution only cares about reproduction and genes, not individuals and their health. The more offspring an individual is able to have, and the more these offspring reproduce themselves, the more successful that individual’s genes become. That’s all that matters from the perspective of natural selection.

For example, if a dog has genes that make it very fertile, and that dog bears or fathers dozens or even hundreds of offspring that survive to adulthood, those genes are going to be carried by those offspring. They too will be very fertile, and over time those “fertility genes” will be the most common in the population. If another dog has genes that make it less fertile, and it only has a few offspring, then those genes will gradually become less common or disappear. 

But what if the fertile dog is so good at reproducing because its body doesn’t bother putting much energy into repairing or maintaining itself? What if nearly all its resources go to reproduction, and that dog gets ill and dies very young? The less fertile dog, in contrast, has a body that is very good at taking care of itself, and it stays healthy and lives twice as long. Shouldn’t evolution favor the healthier dog? 

Unfortunately, evolution favors the dog that reproduces more even if it has a shorter, less healthy life. If the genes that make a dog fertile also makes a dog age fast and die young, these genes will still become more common over time. The dog population would eventually consist mostly of individuals that are shorter-lived but more fertile rather than those with greater lifespan and healthspan who have fewer offspring. 

Of course, humans control much of dog breeding today and most dogs do not evolve with pure natural selection but the legacy of evolutionary history on dog aging is still very much present in modern dogs. This is an oversimplification of a complex and still-evolving idea but it works pretty well as a general explanation of why resilience against age-related deterioration is not favored by evolution. 

Some species do live much longer than others, so there is variation in how evolution shapes different species. Humans, for example, live much longer than many other mammals. Our brains give us our competitive edge, but also require more time to develop and train, giving us less time for reproduction. This tradeoff worked for us but the best strategy for a given species depends on the details of the context in which it evolved.

Victory, with some exceptions, in the evolutionary race has gone to the swift and fertile, not to the slow and enduring.

Aging and evolution

From an evolutionary perspective, it isn’t immediately obvious why animals should experience degeneration and illness as they age. Shouldn’t natural selection favor those who are healthier and live longer? Shouldn’t we eventually evolve to live forever since immortal individuals are clearly more “fit” than those who age?&nbsp;



But evolution only cares about reproduction and genes, not individuals and their health. The more offspring an individual is able to have, and the more these offspring reproduce themselves, the more successful that individual’s genes become. That’s all that matters from the perspective of natural selection.



For example, if a dog has genes that make it very fertile, and that dog bears or fathers dozens or even hundreds of offspring that survive to adulthood, those genes are going to be carried by those offspring. They too will be very fertile, and over time those “fertility genes” will be the most common in the population. If another dog has genes that make it less fertile, and it only has a few offspring, then those genes will gradually become less common or disappear.&nbsp;



But what if the fertile dog is so good at reproducing because its body doesn’t bother putting much energy into repairing or maintaining itself? What if nearly all its resources go to reproduction, and that dog gets ill and dies very young? The less fertile dog, in contrast, has a body that is very good at taking care of itself, and it stays healthy and lives twice as long. Shouldn’t evolution favor the healthier dog?&nbsp;



Unfortunately, evolution favors the dog that reproduces more even if it has a shorter, less healthy life. If the genes that make a dog fertile also makes a dog age fast and die young, these genes will still become more common over time. The dog population would eventually consist mostly of individuals that are shorter-lived but more fertile rather than those with greater lifespan and healthspan who have fewer offspring.&nbsp;



Of course, humans control much of dog breeding today and most dogs do not evolve with pure natural selection but the legacy of evolutionary history on dog aging is still very much present in modern dogs. This is an oversimplification of a complex and still-evolving idea but it works pretty well as a general explanation of why resilience against age-related deterioration is not favored by evolution.&nbsp;



Some species do live much longer than others, so there is variation in how evolution shapes different species. Humans, for example, live much longer than many other mammals. Our brains give us our competitive edge, but also require more time to develop and train, giving us less time for reproduction. This tradeoff worked for us but the best strategy for a given species depends on the details of the context in which it evolved.



Victory, with some exceptions, in the evolutionary race has gone to the swift and fertile, not to the slow and enduring.

Dogs come in an astounding range of shapes and sizes. The smallest breeds, like the Chihuahua and Yorkshire Terrier, have a maximum size of about 6-7 pounds, with many individuals weighing less than this. The largest breeds, such as some varieties of mastiffs, can weigh over 150 pounds even when not overweight. 

This variety in size is greater than that of any other species. Dogs vary so much in size and appearance because of  intensive selective breeding by humans. The genetics of body mass is complex, and an individual’s adult size is determined by combinations of many genes. However, scientists have identified a small number of genes which account for almost half of the variation in body size between dog breeds. The general effect of selective breeding on these genes has been to make dogs smaller than their wolf ancestors.

Dogs breeds vary in more than just body size

These genetic changes don’t only affect body size. Dog breeds differ in many other ways, from body shape and color to temperament and even 

 and lifespan. The net effect of the many genetic changes that distinguish large and small breeds is that the smaller breeds tend to live longer than large and giant breeds. There is a direct, or linear, relationship between size and lifespan, so the larger a breed is, the shorter the average longevity of dogs in that breed.

These differences in lifespan can be very large. Some of the biggest breeds, such as English Mastiffs and Bullmastiffs, and Great Danes live only an average of 7-8 years. In contrast, the smallest breeds, such as the Chihuahua, Miniature Poodle, and Yorkshire Terrier, have an average lifespan longer than 12 years and commonly live well into their teens, almost twice as long as much larger breeds.

Genetics also influence health in aging dogs

In addition to overall differences in lifespan, large and small breeds tend to experience somewhat different age-related health problems, those there is much overlap. Large breeds, for example, are more likely to suffer from musculoskeletal disorders, such as arthritis. Cancer also tends to be a more common cause of death in larger breeds. Smaller breeds, on the other hand, are more likely to experience diseases of the nervous system or metabolic disorders, such as glandular diseases and kidney failure.

It is not completely clear why large dog breeds have shorter lifespan than small dog breeds. One possibility is that they may age faster, accumulating physiologic abnormalities and health problems sooner than smaller dogs. Alternatively, they may experience the same overall health impacts of aging as smaller breeds but be less able to cope with and survive these. Research and debate is ongoing to decide between these possible explanations.

Figure 1. Lifespan negatively scales with adult body mass in male and female dogs

Loyal is studying size and its impact on aging

It is clear, however, that body size and growth rate are key factors, and this gives us hope that we could extend the lifespan and healthspan of large dogs by targeting mechanisms associated with these. We understand the genetic differences between small and large breeds, and we know a lot about the effect of these differences on growth rate and metabolism. Loyal is actively investigating therapies to target possible mechanisms underlying the shortened lifespan of large breeds, and we are planning clinical trials to test these in the near future

While owners can’t change the genetics of our dogs, there are many things we can do to give our pups the longest, healthiest life possible whatever their size. Keeping our dogs at a healthy weight, providing regular 

, and keeping up with regular preventative veterinary care can all help maintain good health and keep our canine companions happy and healthy.

Colin Selman, Daniel H. Nussey, Pat Monaghan, Aging: It’s a Dog’s Life, Current Biology, Volume 23, Issue 10, 2013, Pages R451-R453.

Fan R, Olbricht G, Baker X, Hou C. Birth mass is the key to understanding the negative correlation between lifespan and body size in dogs. Aging (Albany NY). 2016 Dec 8;8(12):3209-3222. 

Galis, F., Van Der Sluijs, I., Van Dooren, T. J. M., Metz, J. A. J., & Nussbaumer, M. (2007). 

large dogs die young? Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 308B(2), 119–126

Kraus, C., Pavard, S., & Promislow, D. E. L. (2013). The Size–Life Span Trade-Off Decomposed: Why Large Dogs Die Young. The American Naturalist, 181(4), 492–505

Rimbault M, Beale HC, Schoenebeck JJ, Hoopes BC, Allen JJ, Kilroy-Glynn P, Wayne RK, Sutter NB, Ostrander EA. Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Res. 2013 Dec;23(12):1985-95. doi: 10.1101/gr.157339.113. Epub 2013 Sep 11. PMID: 24026177; PMCID: PMC3847769.

Why do big dogs have unusually short lifespans compared to small dogs?

Dogs come in an astounding range of shapes and sizes. The smallest breeds, like the Chihuahua and Yorkshire Terrier, have a maximum size of about 6-7 pounds, with many individuals weighing less than this. The largest breeds, such as some varieties of mastiffs, can weigh over 150 pounds even when not overweight.&nbsp;



This variety in size is greater than that of any other species. Dogs vary so much in size and appearance because of&nbsp; intensive selective breeding by humans. The genetics of body mass is complex, and an individual’s adult size is determined by combinations of many genes. However, scientists have identified a small number of genes which account for almost half of the variation in body size between dog breeds. The general effect of selective breeding on these genes has been to make dogs smaller than their wolf ancestors.



<figure class="wp-block-image size-large is-resized"><img loading="lazy" decoding="async" src="https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-1-1024x576.png" alt="" class="wp-image-415" width="1024" height="576" srcset="https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-1-1024x576.png 1024w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-1-300x169.png 300w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-1-768x432.png 768w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-1-1536x864.png 1536w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-1.png 1920w" sizes="(max-width: 1024px) 100vw, 1024px" /><figcaption>Based on Figure 1. Body size and lifespan in dogs in <a href="https://www.cell.com/current-biology/pdf/S0960-9822(13)00413-2.pdf" data-type="URL" data-id="https://www.cell.com/current-biology/pdf/S0960-9822(13)00413-2.pdf">Selman et al (2013)</a></figcaption></figure>



<h2 class="wp-block-heading" id="dogs-breeds-vary-in-more-than-just-body-size">Dogs breeds vary in more than just body size</h2>



These genetic changes don’t only affect body size. Dog breeds differ in many other ways, from body shape and color to temperament and even <a href="https://blog-admin.loyalfordogs.com/healthspan-the-healthy-prime-of-life/">healthspan</a> and lifespan. The net effect of the many genetic changes that distinguish large and small breeds is that the smaller breeds tend to live longer than large and giant breeds. There is a direct, or linear, relationship between size and lifespan, so the larger a breed is, the shorter the average longevity of dogs in that breed.



These differences in lifespan can be very large. Some of the biggest breeds, such as English Mastiffs and Bullmastiffs, and Great Danes live only an average of 7-8 years. In contrast, the smallest breeds, such as the Chihuahua, Miniature Poodle, and Yorkshire Terrier, have an average lifespan longer than 12 years and commonly live well into their teens, almost twice as long as much larger breeds.



<h2 class="wp-block-heading" id="genetics-also-influence-health-in-aging-dogs"> Genetics also influence health in aging dogs</h2>



In addition to overall differences in lifespan, large and small breeds tend to experience somewhat different age-related health problems, those there is much overlap. Large breeds, for example, are more likely to suffer from musculoskeletal disorders, such as arthritis. Cancer also tends to be a more common cause of death in larger breeds. Smaller breeds, on the other hand, are more likely to experience diseases of the nervous system or metabolic disorders, such as glandular diseases and kidney failure.



It is not completely clear why large dog breeds have shorter lifespan than small dog breeds. One possibility is that they may age faster, accumulating physiologic abnormalities and health problems sooner than smaller dogs. Alternatively, they may experience the same overall health impacts of aging as smaller breeds but be less able to cope with and survive these. Research and debate is ongoing to decide between these possible explanations.



<figure class="wp-block-image size-large is-resized"><img loading="lazy" decoding="async" src="https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-2-1024x576.png" alt="" class="wp-image-416" width="1022" height="575" srcset="https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-2-1024x576.png 1024w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-2-300x169.png 300w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-2-768x432.png 768w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-2-1536x864.png 1536w, https://blog-admin.loyalfordogs.com/wp-content/uploads/2022/09/Big-vs-small-2.png 1920w" sizes="(max-width: 1022px) 100vw, 1022px" /><figcaption>Based on Figure 1. Lifespan negatively scales with adult body mass in male and female dogs in <a href="https://www.aging-us.com/article/101081/text" data-type="URL" data-id="https://www.aging-us.com/article/101081/text">Fan et al (2016)</a></figcaption></figure>



<h2 class="wp-block-heading" id="loyal-is-studying-size-and-its-impact-on-aging">Loyal is studying size and its impact on aging</h2>



It is clear, however, that body size and growth rate are key factors, and this gives us hope that we could extend the lifespan and healthspan of large dogs by targeting mechanisms associated with these. We understand the genetic differences between small and large breeds, and we know a lot about the effect of these differences on growth rate and metabolism. Loyal is actively investigating therapies to target possible mechanisms underlying the shortened lifespan of large breeds, and we are planning clinical trials to test these in the near future



While owners can’t change the genetics of our dogs, there are many things we can do to give our pups the longest, healthiest life possible whatever their size. Keeping our dogs at a healthy weight, providing regular <a href="https://blog-admin.loyalfordogs.com/dog-enrichment-activities-healthy-brains-and-happy-dogs/">exercise and behavioral enrichment</a>, and keeping up with regular preventative veterinary care can all help maintain good health and keep our canine companions happy and healthy.



Sources



Colin Selman, Daniel&nbsp;H. Nussey, Pat Monaghan, Aging: It’s a Dog’s Life, Current Biology, Volume 23, Issue 10, 2013, Pages R451-R453.



Fan R, Olbricht G, Baker X, Hou C. Birth mass is the key to understanding the negative correlation between lifespan and body size in dogs. Aging (Albany NY). 2016 Dec 8;8(12):3209-3222.&nbsp;



Galis, F., Van Der Sluijs, I., Van Dooren, T. J. M., Metz, J. A. J., &amp; Nussbaumer, M. (2007).&nbsp;Do large dogs die young? Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 308B(2), 119–126



Kraus, C., Pavard, S., &amp; Promislow, D. E. L. (2013).&nbsp;The Size–Life Span Trade-Off Decomposed: Why Large Dogs Die Young. The American Naturalist, 181(4), 492–505.



Rimbault M, Beale HC, Schoenebeck JJ, Hoopes BC, Allen JJ, Kilroy-Glynn P, Wayne RK, Sutter NB, Ostrander EA. Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Res. 2013 Dec;23(12):1985-95. doi: 10.1101/gr.157339.113. Epub 2013 Sep 11. PMID: 24026177; PMCID: PMC3847769.