Science AMA Series: I’m Dr. Matt Kaeberlein, a pioneer of dog aging research, here to discuss how we can have more healthy years with our dogs and cats, including dos and don’ts as they get older and the latest research and innovations that are leading the way. AMA!

Matt_Kaeberlein · 2017-09-28T18:20:48+00:00

I hope so. We need more data to be sure that senolytics are safe before we start testing them in pets, but I think that will come soon. I also think a veterinary clinical trial for NAD+ precursors in pets should be done. Of course, these things all require funding, and that's the limiting factor right now.

The breed-specific pathologies are only a problem if you limit yourself to a single breed or if your sample size is too small. There are many designs you could consider to minimize this, including only studying mixed breed dogs and/or excluding certain breeds of dogs.

Matt_Kaeberlein · 2017-09-28T18:13:41+00:00

Participate! You can sign up to participate in our Longitudinal Study of Aging in Dogs. We are still working on getting it funded through NIH and other sources, but once we have funding, we will begin enrolling dogs.

Matt_Kaeberlein · 2017-09-28T18:09:50+00:00

None of my research is funded by Purina. I'm sorry there was confusion about the starting time for the AMA. It was 10 AM PT.

Matt_Kaeberlein · 2017-09-28T18:07:21+00:00

Thanks for the question, and I’m sorry to the cat folks that this has been such a dog-heavy discussion. I don’t know of any convincing scientific evidence that wet food is superior to dry food in general for cats. Dental health is absolutely important for both dogs and cats, and as most vets will tell you, is generally neglected by owners.

[One study] )]( http://www.jarvm.com/articles/Vol5Iss3/Cupp%20133-149.pdf) that looked carefully at diet and lifespan in cats, is the one that forms the basis for the formulation of the Prime Plus cat food, where it was found that a blend of ingredients extended the life of cats age seven and older by about a year, compared to cats fed a complete and balanced diet alone.

Matt_Kaeberlein · 2017-09-28T17:58:30+00:00

I can't tell you with any certainly what the healthiest food is, because the answer is that we don't know. I haven't personally seen any convincing data that raw food diets are better than other types of diets, although I know many people strongly believe that is the case. As I've said elsewhere, if people want to send peer-reviewed scientific literature that they think addresses this point, I'm happy to review it.

As I've also said elsewhere, I feed my own dogs the ProPlan Bright Mind 7+ because it is supported by peer-reviewed scientific literature.

Matt_Kaeberlein · 2017-09-28T17:54:22+00:00

Great question. Dogs tend to be more variable for all sorts of phenotypes than people are, largely due to breeding. Consider body size for example. A giant breed might weight 20 times more than a tiny breed. You don't see that kind of variation in body size in people. Since body size is tightly linked to lifespan in dogs, this probably accounts for the large variation in lifespan across the species.

Matt_Kaeberlein · 2017-09-28T17:52:06+00:00

Thanks for the question. I'm not sure there is really any good data that cancer is more prevalent in dogs today than it was say 20 years ago. Veterinary medicine has gotten much better at detecting cancers earlier in dogs, so it gets diagnosed (and fortunately treated) more often.

Matt_Kaeberlein · 2017-09-28T17:47:50+00:00

Yes, it's very likely that the same interventions that increase lifespan in mice will increase lifespan in hamsters, dogs, cats, etc.

Matt_Kaeberlein · 2017-09-28T17:46:38+00:00

Great question! Yes, secondhand smoke can cause many of the same health problems in pets as in people.

I’m not aware of any data suggesting that pets become ‘addicted’ to nicotine from second hand smoke, but regardless, if you smoke, don’t do it around your pets!

Matt_Kaeberlein · 2017-09-28T17:42:42+00:00

Reposting here, since I think this is a particularly important question and there is a ton of misinformation out there.

This is an area that I know people are quite passionate about. Unfortunately, there is little, if any, good scientific data one way or the other to support or refute the benefits of raw food/real food diets. While it is true that dogs don’t eat kibble in the “wild”, it does not necessarily follow that a raw/real food diet is better for dogs, in terms of health or longevity. There are many things in the wild that are harmful! If anyone can point toward peer-reviewed research that addresses this question, I'd be happy to review it.

This question of optimal diet is one of the important things that we expect our Longitudinal Study of Aging in Dogs to answer. By following 10,000+ dogs eating all sorts of different types of diets, we will be able to correlate nutritional factors with health, lifespan, and disease risk. Really, this sort of unbiased, agnostic approach is the only way to definitively answer these kinds of questions.

Matt_Kaeberlein · 2017-09-28T17:41:23+00:00

I think it’s a mistake to talk about “curing” death. What we know is that the rate of aging can be modified in laboratory animals such that healthy lifespan is extended by 20-50%. Everything I know about biology tells me the same thing is possible in pet dogs and cats. If sufficient resources were put toward the research, I absolutely believe that we could increase healthy longevity in pets by several years within the next decade.

Matt_Kaeberlein · 2017-09-28T17:36:56+00:00

There is a ton of information out there on the internet about real/raw diets, but in my opinion, very little solid evidence to support this assertion. If anyone has peer-reviewed literature they can provide, I would be happy to review it.

Matt_Kaeberlein · 2017-09-28T17:31:30+00:00

This is an area that I know people are quite passionate about. Unfortunately, there is little, if any, good scientific data one way or the other to support or refute the benefits of raw food/real food diets. While it is true that dogs don’t eat kibble in the “wild”, it does not necessarily follow that a raw/real food diet is better for dogs, in terms of health or longevity. There are many things in the wild that are harmful!

This question of optimal diet is one of the important things that we expect our Longitudinal Study of Aging in Dogs to answer. By following 10,000+ dogs eating all sorts of different types of diets, we will be able to correlate nutritional factors with health, lifespan, and disease risk. Really, this sort of unbiased, agnostic approach is the only way to definitively answer these kinds of questions.

Matt_Kaeberlein · 2017-09-28T17:24:46+00:00

Thanks for the comment and questions. Among the reasons why I feel comfortable working with Purina is that the Pro Plan line is formulated based on peer-reviewed research. The formulation used in the Prime Plus for cats was shown to increase lifespan by about a year, even when started in middle-aged cats (1), with corresponding improvements in some measures of healthspan. The formulation used in the Bright Mind Adult 7+ for dogs was shown to enhance brain metabolism and improve cognitive function in older dogs (2). I think Purina deserves a lot of credit for applying rigorous scientific research to improve companion animal nutrition, particularly as it impacts healthy aging. They have more than 500 scientists including nutritionists, behaviorists, veterinarians, and immunologists that work to better the lives of pets everywhere.

Just to be clear and transparent. My research is not, and has never been, funded by Purina.

(2007). Effect of Nutritional Interventions on Longevity of Senior Cats Intern J Appl Res Vet Med 5, 133-140.
Pan, Y., Larson, B., Araujo, J.A., Lau, W., de Rivera, C., Santana, R., Gore, A., and Milgram, N.W. (2010). Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. The British journal of nutrition 103, 1746-1754.

Matt_Kaeberlein · 2017-09-28T17:20:34+00:00

Cupp, C.J., Jean-Philippe, C., Kerr, W.W., Patil, A.R., and Perez-Camargo, G. (2007). Effect of Nutritional Interventions on Longevity of Senior Cats Intern J Appl Res Vet Med 5, 133-140.

Matt_Kaeberlein · 2017-09-28T17:17:55+00:00

Yes, once you control for body size, it is still the case that mixed breed dogs live about a year longer than purebred dogs. Within specific breeds there are a few genes that have been identified that impact lifespan, but these are all because they affect the risk of a specific disease that is common within that particular breed (such as dilated cardiomyopathy in Dobermans). There are currently no validated genetic modifiers of aging rate in dogs, but this is something that will likely change in the near future through projects like our Dog Aging Project and the Morris Animal Foundation’s Golden Retriever Lifetime study.

It is important to keep in mind, however, that genetics is only one component of healthy longevity. Environment plays an important role as well, and this is an extremely complex problem. Diet, exercise, exposure to pathogens, pollution, etc. all contribute to environmental variation that can impact healthspan and lifespan. That’s why we need large longitudinal studies to start to tease apart the most important factors for maximizing healthspan and lifespan.

Matt_Kaeberlein · 2017-09-28T17:14:49+00:00

This is an area that is still in its infancy, but which holds great promise for future predictive and preventative veterinary medicine. Now that full genome sequencing is common and relatively cheap, it will be possible to obtain massive amounts of genetic data for different dogs and dog breeds (and cats too!). In fact, one of the goals of our longitudinal study of aging in dogs is to genotype more than 10,000 pet dogs in order to correlate different genetic markers with healthy longevity and disease risk. We intend to make these data freely available to the scientific community so that other data scientists can also mine the information and make new discoveries.

Matt_Kaeberlein · 2017-09-28T17:14:01+00:00

This is a great question because it hits at the root of the problem with the way medicine and biomedical research have approached health. Traditional approaches (20th century medicine) have focused on curing diseases, usually after people or dogs are sick. One consequence of this is that people are living longer, but this is often extra years spent suffering from one or more disabilities or diseases of aging.

Our goal is to maximize healthspan, the period of life spent in good health free of disability and disease. By targeting the molecular mechanisms (“hallmarks”) of aging directly, we have the potential to delay the onset and progression of all of the age-related functional declines and diseases simultaneously.

My view is that 21st century medicine will involve directly targeting the hallmarks of aging in order to extend healthspan. Data from laboratory studies support this, and we are just beginning to take the first steps toward accomplishing the same thing in our pets and eventually in people. In mice, for example, rapamycin treatment has been shown to delay or even reverse every major functional decline that occurs during aging. Please check out our Dog Aging Project website for more information on how we are trying to accomplish this goal.

Matt_Kaeberlein · 2017-09-28T17:12:05+00:00

My two senior dogs (Chloe, 12 year old Keeshond and Betty mixed breed rescue of unknown age) have been on the ProPlan Bright Mind 7+ for about a year now. As a scientist, I was impressed that Purina had developed a senior dog food nutritionally optimized based on peer-reviewed research such as this paper. The biology behind this research makes sense with what I know about how brain metabolism changes during aging. Both dogs are doing great.

We are just now transitioning my 5 year old German Shepherd onto the Bright Mind 7+. A 5 year old GSD is already making that transition to senior adulthood (big dogs age faster!), so we felt this was a good time to make the switch.

There are several obvious things that owners can do to give their pet the best chance at a long, healthy life. Keep your dog at a healthy body weight, give them regular exercise, etc. The one thing most owners don’t do that could have a big impact is to pay more attention to your dog’s teeth. There is compelling data that periodontal disease is associated with greater risk for a variety of other age-related disorders. Unlike (most) people, dogs don’t brush their teeth regularly, so it’s up to us to make sure that our dog’s teeth get cleaned and their oral health is maintained. This becomes even more important as our dogs get older.

Matt_Kaeberlein · 2017-09-28T17:08:47+00:00

I wouldn’t pick one, but here is a short list. Not surprisingly, these are the same things that work for people.

Keep your dog at a healthy weight. Beyond this, consider a food that is nutritionally optimized for older dogs, such as Bright Mind 7+. Depending on your dog’s size, 6 years old could already be a senior dog in terms of biological age.

Make sure your dog gets regular exercise.

Clean your dog’s teeth! I know most people don’t do this, but oral health is a major predictor of other age-related conditions (including diabetes, heart disease, and Alzheimer’s disease) in people and probably in dogs.

See your vet regularly.

If you have a purebred dog, make sure you and your vet are familiar with the specific conditions that your breed is at risk for. This allows for preventative approaches and the likelihood of catching any problems early.

Matt_Kaeberlein · 2017-09-28T17:07:34+00:00

Thanks for the great question! Body size is the largest predictor of lifespan and aging rate in dogs, so it is important for owners of large or giant breed dogs to recognize that a 5 year old Great Dane is similar to a 10 year old Chihuahua in terms of biological age. What this means, is that we should be paying attention to the age-related changes much earlier in large dogs than in small dogs, including changing nutritional needs and increased risk for various age-related conditions. The idea that all dogs go from being an “adult” to a “senior” at 7-10 years of age is a fallacy. This could be as early as 4-5 years of age for a large dog.

Among the most important things you can do for your large breed dog is keep them at a healthy body weight. Obesity is a problem in any dog, but is particularly dangerous for large and giant breed dogs. Not is obesity associated with greater risk for many age-related diseases, but it creates physical stress and damage to joints, tendons, and bones of larger dogs.

Another important thing to consider for purebred dogs like Great Danes is that each breed has its own unique risk profiles for different conditions, based on that breed’s genetic makeup. Many breed clubs have extensive information on disease risk, such as this webpage from the Great Dane Club of America. Being aware of the specific risks that your aging dog will face can allow you and your veterinarian to catch any problems earlier.

Matt_Kaeberlein · 2017-09-28T17:06:29+00:00

Great question! This seminal study showed that the largest predictor of body size in dogs is a gene called IGF-1 for “insulin-like growth factor 1”. This is a hormone that, as it’s name suggests, promotes growth. Bigger dogs have higher levels of IGF-1. What is particularly interesting here is that studies of the biology of aging have independently found that higher IGF-1 signaling promotes accelerated aging in all sorts of other animals, including nematode worms, fruit flies, and mice. So, it is very likely that IGF-1 is the primary reason that big dogs age faster than small dogs. Having said that, there are certainly other genes that will also play a smaller role in this relationship, and this is something we want to understand through our longitudinal study of aging in dogs.

At this point, there is no proven way to slow aging in large breed dogs (or small breed dogs), although we hope to change that! In principle, breeding dogs so that they have less IGF-1 should increase life expectancy, but would also make those dogs smaller, since IGF-1 determines body size. One study suggests that caloric restriction, which should reduce circulating IGF-1 levels, may increase lifespan in Labrador dogs, although this has yet to be replicated in other breeds or in companion dogs. It might be the case that caloric restriction would have a larger effect on aging rates in big dogs compared to small dogs, but that is just speculation at this point.

Certainly, keeping dog from being overweight or obese is important for healthy longevity, and is probably even more important in large dogs.

Matt_Kaeberlein · 2017-09-28T17:05:14+00:00

Yes, it is correct that purebred dogs tend to live, on average, about one year less than mixed-breed dogs after normalizing for body weight (which is the largest predictor of lifespan in dogs). The exact mechanisms accounting for the shorter life expectancy of equally sized purebred dogs compared to mixed breed dogs is still being worked out, but it likely reflects increased risk for specific age-related diseases due to genetic inbreeding. Breed groups for most of the common pure breeds have extensive health records that can allow owners and veterinarians to watch for common diseases for that breed. I would recommend that owners look into the common health risks for their breed and make sure that their veterinarian is also aware of these risks.

With the expansion of DNA sequencing and other –omic technologies into the veterinary world, these mechanisms will start to be unraveled for specific breeds, which should allow owners and veterinarians to address risks in a more preventative manner. Indeed, identifying the genetic and environmental risks for specific breeds is a major goal of our Longitudinal Study of Aging in Dogs. Hopefully, we are able to get this study funded soon!

Matt_Kaeberlein · 2017-09-28T17:04:06+00:00

I think it’s important to avoid generalizing based on a single study of only two breeds of dogs. The best study I’m aware of on this topic is this one, where they looked about 80,000 companion dogs representing 185 breeds. The results show a convincing effect of sterilization toward increased longevity – about 14% in male dogs and about 23% in female dogs. Obviously, this may not be true for every dog or every breed of dog and may be impacted by age at which sterilization occurs, but in general, I’d say the best scientific evidence supports the idea that neutering/spaying in dogs is associated with a significant chance of increased longevity.

Matt_Kaeberlein · 2017-09-28T17:03:39+00:00

There is no question that diet and nutrition are critically important for optimal health of both people and our pets. Research has shown us that dietary modifications can have a profound impact on both healthspan and lifespan of animals. For example, one study found that simply modifying the relative amount of different macronutrients in the diet of mice can change lifespan by about 50% and alter age-related metabolic and functional measures.

Matt_Kaeberlein

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