Scientists Are Studying How to Help Dogs Have Longer Lives, in a Bid to Further Our Own
Feeding dogs only once a day is showing health benefits in a large study, scientists report.
The sad eyes. The wagging tail. The frustrated whine. The excited bark. Dogs know how to get their owners to fork over the food more often.
The extra calories dogs get from feeding patterns now used by many Americans may not be good for them from a health and longevity viewpoint. In research from a large study called the Dog Aging Project, canines fed once a day had better scores on cognition tests and lower odds of developing diseases of organs throughout the body: intestinal tract, mouth and teeth, bones and joints, kidneys and bladder, and liver and pancreas.
Fewer than 1 in 10 dog owners fed their furry friends once daily, while nearly three fourths provided two daily meals.
“Most veterinarians have been led to believe that feeding dogs twice a day is optimal, but this is a relatively new idea that has developed over the past few decades with little supportive evidence from a health standpoint,” said Matt Kaeberlein, PhD, Co-Director of the Dog Aging Project, a professor of pathology and Director of the Healthy Aging and Longevity Research Institute at the University of Washington. Kaeberlein studies basic mechanisms of aging to find ways of extending the healthspan, the number of years of life lived free of disease. It’s not enough to extend the lifespan unless declines in biological function and risks of age-related diseases are also studied, he believes, hence the healthspan.
The Dog Aging Project is studying tens of thousands of dogs living with their owners in the real world, not a biology laboratory. The feeding study is the first of several reports now coming from the project based on owners’ annual reports of demographics, physical activity, environment, dog behavior, diet, medications and supplements, and health status. It has been posted on bioRxiv as it goes through peer review.
“All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans. It just happens much faster in dogs.”
“The Dog Aging Project is one of the most exciting in the longevity space,” said David A. Sinclair, professor in the Department of Genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. “Not only is it important to help our companions live longer and healthier, but because they are like people and share the same environment and many of the lifestyles as their owners, they are the perfect model for human longevity interventions.”
The epigenetic clock — and specifically changes in gene expression resulting from methylation of cytosine and guanine in the DNA — provides the critical connection between aging in dogs and people. “All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans,” Kaeberlein said. “It just happens much faster in dogs.” These methylation changes, called the “methylomes,” have been associated with rates of aging in dogs, humans, and also mice.
In a 2020 study young dogs matched with young adults and aged dogs matched with older adults showed the greatest similarities in methylomes. In the Cell Systems report, Tina Wang of the University of California, San Diego, and colleagues wrote that the methylome “can be used to quantitatively translate the age-related physiology experienced by one organism (i.e., a model species like dog) to the age at which physiology in a second organism is most similar (i.e., a second model or humans).” This allows rates of aging in one species to be mapped onto aging in another species, providing “a compelling tool in the quest to understand aging and identify interventions for maximizing healthy lifespan.”
In the Dog Aging Project study, 8% of 24,238 owners fed their dogs once daily, the same as the percentage of owners serving three daily meals. Twice-daily feedings were most common (73%), and just over 1 in 10 owners (11%) “free fed” their dogs by just filling up the bowl whenever it was empty — most likely Rover’s favorite option.
“The notion of breakfast, lunch, and dinner for people in the United States is not based on large studies that compared three meals a day to two meals a day, or to four, “ said Kate E. Creevy, chief veterinary officer with the Dog Aging Project and associate professor at Texas A&M University. “It’s more about what we are accustomed to. Similarly, there are not large population studies comparing outcomes of dogs fed once, twice, or three times a day.”
“We do not recommend that people change their dogs’ diets based on this report,” Creevy emphasized. “It’s important to understand the difference between research that finds associations versus research that finds cause and effect.”
To establish cause and effect, the Dog Aging Project will follow their cohort over many years. Then, Creevy said, “We will be able to determine whether the associations we have found with feeding frequency are causes, or effects, or neither.”
While not yet actionable, the feeding findings fit with biology across a variety of animals, Kaeberlein said, including indicators that better health translates into longer healthspans. He said that caloric restriction and perhaps time-restricted eating or intermittent fasting — all ways that some human diets are structured — can have a positive impact on the biology of aging by allowing the gastrointestinal tract to have time each day to rest and repair itself, just as sleep benefits the brain through rest.
Timing of meals is also related to the concept of ketogenesis, Kaeberlein explained. Without access to glucose, animals switch over to a ketogenic state in which back-up systems produce energy through metabolic pathways that generate ketones. Mice go into this state very quickly, after a few hours or an overnight fast, while people shift to ketogenesis more slowly, from a few hours to up to 36 hours for people on typical Western diets, Kaeberlein said.
Dogs are different. They take at least two days to shift to ketogenesis, suggesting they have evolved to need fewer meals that are spaced out rather than the multiple daily meals plus snacks that people prefer.
As this relates to longevity, Kaeberlein said that a couple of studies show that mice who are fed a ketogenic diet have longer lifespans (years of life regardless of health). “For us, the next step is to analyze the composition of the dogs’ diets or the relationship of multiple daily feedings with obesity,” he said. “Maybe not being obese is related to better health.”
To learn more, the Dog Aging Project needs dogs — lots of dogs! Kaeberlein wants at least 100,000 dogs, including small dogs, large dogs, dogs of all ages. Puppies are needed for the researchers to follow across their lifespan. The project has an excellent website where owners can volunteer to participate.
Nutritional strategies are often not built around sound scientific principles, Kaeberlein said. In human nutrition, people have tried all kinds of diets over the years, including some that were completely wrong. Kaeberlein and his colleagues in the Dog Aging Project want to change that, at least for people’s canine companions, and hopefully, as a result, give dogs added years of healthy life and provide clues for human nutrition.
After that, maybe they can do something about those sad eyes and the frustrated whine.
Gene Transfer Leads to Longer Life and Healthspan
In August, a study provided the first proof-of-principle that genetic material transferred from one species to another can increase both longevity and healthspan in the recipient animal.
The naked mole rat won’t win any beauty contests, but it could possibly win in the talent category. Its superpower: fighting the aging process to live several times longer than other animals its size, in a state of youthful vigor.
It’s believed that naked mole rats experience all the normal processes of wear and tear over their lifespan, but that they’re exceptionally good at repairing the damage from oxygen free radicals and the DNA errors that accumulate over time. Even though they possess genes that make them vulnerable to cancer, they rarely develop the disease, or any other age-related disease, for that matter. Naked mole rats are known to live for over 40 years without any signs of aging, whereas mice live on average about two years and are highly prone to cancer.
Now, these remarkable animals may be able to share their superpower with other species. In August, a study provided what may be the first proof-of-principle that genetic material transferred from one species can increase both longevity and healthspan in a recipient animal.
There are several theories to explain the naked mole rat’s longevity, but the one explored in the study, published in Nature, is based on the abundance of large-molecule high-molecular mass hyaluronic acid (HMM-HA).
A small molecule version of hyaluronic acid is commonly added to skin moisturizers and cosmetics that are marketed as ways to keep skin youthful, but this version, just applied to the skin, won’t have a dramatic anti-aging effect. The naked mole rat has an abundance of the much-larger molecule, HMM-HA, in the chemical-rich solution between cells throughout its body. But does the HMM-HA actually govern the extraordinary longevity and healthspan of the naked mole rat?
To answer this question, Dr. Vera Gorbunova, a professor of biology and oncology at the University of Rochester, and her team created a mouse model containing the naked mole rat gene hyaluronic acid synthase 2, or nmrHas2. It turned out that the mice receiving this gene during their early developmental stage also expressed HMM-HA.
The researchers found that the effects of the HMM-HA molecule in the mice were marked and diverse, exceeding the expectations of the study’s co-authors. High-molecular mass hyaluronic acid was more abundant in kidneys, muscles and other organs of the Has2 mice compared to control mice.
In addition, the altered mice had a much lower incidence of cancer. Seventy percent of the control mice eventually developed cancer, compared to only 57 percent of the altered mice, even after several techniques were used to induce the disease. The biggest difference occurred in the oldest mice, where the cancer incidence for the Has2 mice and the controls was 47 percent and 83 percent, respectively.
With regard to longevity, Has2 males increased their lifespan by more than 16 percent and the females added 9 percent. “Somehow the effect is much more pronounced in male mice, and we don’t have a perfect answer as to why,” says Dr. Gorbunova. Another improvement was in the healthspan of the altered mice: the number of years they spent in a state of relative youth. There’s a frailty index for mice, which includes body weight, mobility, grip strength, vision and hearing, in addition to overall conditions such as the health of the coat and body temperature. The Has2 mice scored lower in frailty than the controls by all measures. They also performed better in tests of locomotion and coordination, and in bone density.
Gorbunova’s results show that a gene artificially transferred from one species can have a beneficial effect on another species for longevity, something that had never been demonstrated before. This finding is “quite spectacular,” said Steven Austad, a biologist at the University of Alabama at Birmingham, who was not involved in the study.
Just as in lifespan, the effects in various organs and systems varied between the sexes, a common occurrence in longevity research, according to Austad, who authored the book Methuselah’s Zoo and specializes in the biological differences between species. “We have ten drugs that we can give to mice to make them live longer,” he says, “and all of them work better in one sex than in the other.” This suggests that more attention needs to be paid to the different effects of anti-aging strategies between the sexes, as well as gender differences in healthspan.
According to the study authors, the HMM-HA molecule delivered these benefits by reducing inflammation and senescence (cell dysfunction and death). The molecule also caused a variety of other benefits, including an upregulation of genes involved in the function of mitochondria, the powerhouses of the cells. These mechanisms are implicated in the aging process, and in human disease. In humans, virtually all noncommunicable diseases entail an acceleration of the aging process.
So, would the gene that creates HMM-HA have similar benefits for longevity in humans? “We think about these questions a lot,” Gorbunova says. “It’s been done by injections in certain patients, but it has a local effect in the treatment of organs affected by disease,” which could offer some benefits, she added.
“Mice are very short-lived and cancer-prone, and the effects are small,” says Steven Austad, a biologist at the University of Alabama at Birmingham. “But they did live longer and stay healthy longer, which is remarkable.”
As for a gene therapy to introduce the nmrHas2 gene into humans to obtain a global result, she’s skeptical because of the complexity involved. Gorbunova notes that there are potential dangers in introducing an animal gene into humans, such as immune responses or allergic reactions.
Austad is equally cautious about a gene therapy. “What this study says is that you can take something a species does well and transfer at least some of that into a new species. It opens up the way, but you may need to transfer six or eight or ten genes into a human” to get the large effect desired. Humans are much more complex and contain many more genes than mice, and all systems in a biological organism are intricately connected. One naked mole rat gene may not make a big difference when it interacts with human genes, metabolism and physiology.
Still, Austad thinks the possibilities are tantalizing. “Mice are very short-lived and cancer-prone, and the effects are small,” he says. “But they did live longer and stay healthy longer, which is remarkable.”
As for further research, says Austad, “The first place to look is the skin” to see if the nmrHas2 gene and the HMM-HA it produces can reduce the chance of cancer. Austad added that it would be straightforward to use the gene to try to prevent cancer in skin cells in a dish to see if it prevents cancer. It would not be hard to do. “We don’t know of any downsides to hyaluronic acid in skin, because it’s already used in skin products, and you could look at this fairly quickly.”
“Aging mechanisms evolved over a long time,” says Gorbunova, “so in aging there are multiple mechanisms working together that affect each other.” All of these processes could play a part and almost certainly differ from one species to the next.
“HMM-HA molecules are large, but we’re now looking for a small-molecule drug that would slow it’s breakdown,” she says. “And we’re looking for inhibitors, now being tested in mice, that would hinder the breakdown of hyaluronic acid.” Gorbunova has found a natural, plant-based product that acts as an inhibitor and could potentially be taken as a supplement. Ultimately, though, she thinks that drug development will be the safest and most effective approach to delivering HMM-HA for anti-aging.
A new study provides key insights in what causes Alzheimer's: a breakdown in the brain’s system for clearing waste.
In recent years, researchers of Alzheimer’s have made progress in figuring out the complex factors that lead to the disease. Yet, the root cause, or causes, of Alzheimer’s are still pretty much a mystery.
In fact, many people get Alzheimer’s even though they lack the gene variant we know can play a role in the disease. This is a critical knowledge gap for research to address because the vast majority of Alzheimer’s patients don’t have this variant.
A new study provides key insights into what’s causing the disease. The research, published in Nature Communications, points to a breakdown over time in the brain’s system for clearing waste, an issue that seems to happen in some people as they get older.
Michael Glickman, a biologist at Technion – Israel Institute of Technology, helped lead this research. I asked him to tell me about his approach to studying how this breakdown occurs in the brain, and how he tested a treatment that has potential to fix the problem at its earliest stages.
Dr. Michael Glickman is internationally renowned for his research on the ubiquitin-proteasome system (UPS), the brain's system for clearing the waste that is involved in diseases such as Huntington's, Alzheimer's, and Parkinson's. He is the head of the Lab for Protein Characterization in the Faculty of Biology at the Technion – Israel Institute of Technology. In the lab, Michael and his team focus on protein recycling and the ubiquitin-proteasome system, which protects against serious diseases like Alzheimer’s, Parkinson’s, cystic fibrosis, and diabetes. After earning his PhD at the University of California at Berkeley in 1994, Michael joined the Technion as a Senior Lecturer in 1998 and has served as a full professor since 2009.
Dr. Michael Glickman