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Why studying the health of our dogs could help humans ward off old age

Frisbee is part German shepherd, chow chow and cocker spaniel, with a sprinkle of another indeterminate breed. 

Although she appears to be very happy with life — she rolls on to her side with a contented sigh, her nose twitching on constant high alert for the scent of food — at the grand old age of 16, she has amassed a lengthy list of health conditions.

Her eyes are clouded with cataracts, she has stiff, arthritic joints and digestive problems caused by a malfunctioning pancreas, which means she must eat little and often. 

And from the way she studiously ignores the calls of her owner, Dr Daniel Promislow, it seems her hearing isn’t as sharp as it once was either.

It is to be expected: if Frisbee was a human, she’d be in her 90s (with a medium-sized dog, their first year roughly equals 15 human years, their second, nine human years and thereafter every year notches up five human years). 

Many of the conditions and diseases that affect older dogs are the same as those that affect older humans — as well as fading hearing and eyesight, they can develop osteoarthritis, heart disease, dementia and kidney disease.

Dogs also get cancer at roughly the same rate as humans.

Matt Kaeberlein, PhD, professor of pathology, with his dog Dobby. One of the things rapamycin does is turn down the chronic inflammatory state that goes along with ageing, ‘referred to as inflammaging’, says Dr Kaeberlein

And now Dr Promislow, a professor of biology, medicine and pathology at the University of Washington School of Medicine in the U.S., has joined a team of scientists investigating these parallels in a unique study.

The Dog Aging Project aims to make the most of these shared diseases in the hope that it can lead to improvements not just in canine health but human health, too.

This isn’t about subjecting dogs to tests in labs.

This study involves monitoring pet dogs in their own homes to see how their environments, lifestyles and diets impact on how they age and their risk of age-related diseases. 

Not only that but the scientists are also trialling a medicine which they believe will extend dogs’ lifespans by as much as a third — and again, they say the results could benefit humans.

For, despite appearances otherwise, we are closely bound to dogs. ‘Evolutionarily, humans are closer to mice than dogs, but we share more genetically with dogs than mice,’ says Dr Promislow.

‘Humans and dogs shared a common ancestor about 94 million years ago, while humans and mice shared a common ancestor a bit more recently, around 89 million years ago. However, because of their shorter generation time, mice have undergone more genetic changes than dogs since then.

‘So even though dogs and humans are more evolutionarily distant than dogs and mice, the difference between a dog and a human is likely to be less than the difference between a mouse and a human.’

But what really makes dogs important for this research is that they live alongside us. ‘Dogs share our environment — they share our homes and, to a certain extent, our lifestyles,’ says Dr Promislow.

They breathe the same air, drink the same water and get exposed to the same levels of pollution. ‘While it is hard to monitor people for 70 years to see what impact all that has on health and the risk of diseases, with dogs we can monitor them from when they are a puppy to late life — and that will happen over ten years or so,’ adds Dr Promislow. ‘So we can see how their environment or lifestyle affects them relatively quickly.’

Like Dr Promislow, he is a proud dog owner and says of his 11-year old German shepherd, Dobby: ¿I love him so much ¿ and that makes this work personal to me. The science is important but it¿s also important to have more time with our dogs, who are like family members.¿

Like Dr Promislow, he is a proud dog owner and says of his 11-year old German shepherd, Dobby: ‘I love him so much — and that makes this work personal to me. The science is important but it’s also important to have more time with our dogs, who are like family members.’

The study won’t be looking just at visible signs of ageing but also at the changes at a cellular level, as well as the role of genes. One of the things it will focus on is the DNA of exceptionally long-lived dogs, the ‘super-centenarians’. The study is a massive under-taking — in two years the team has recruited 36,000 pet owners and hopes to make that 100,000 soon.

So far, recruits are limited to the U.S. but the plan is to extend it to other countries, including the UK.

The project, which is funded mainly by the National Institute on Aging, part of the U.S. National Institutes of Health, was initially launched in 2019 by Dr Promislow, Dr Matt Kaeberlein, a professor of laboratory medicine and pathology at Washington University, and Kate Creevy, a professor at the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University.

Dr Promislow has spent his career investigating ageing, much of it working with fruit flies — but his eureka moment to move into dog research came when, in 2007, he saw a magazine cover featuring a picture of a Great Dane alongside a chihuahua.

The picture was related to a piece about how a single gene, IGF1 [insulin-like growth factor 1], accounts for the huge amount of variation in the size of dogs.

It is thought changes in this gene determine how much growth factor is produced and so determines how big the dog becomes.

‘This gene is thought to be important in flies, mice, even humans,’ says Dr Promislow. ‘So it got me wondering, if that gene is so important in size, might it be related to lifespan? The unusual thing about dogs is that the large breeds are not long-lived — while usually, with mammals, the bigger they are the longer they live. Look at whales, for example.’

Dr Promislow was working at Georgia University and there met Kate Creevy, who also saw the potential for studying dog ageing. They joined forces with Dr Kaeberlein after Dr Promislow moved to Washington.

To join the project, pet owners fill in a detailed questionnaire about themselves, their dogs and their homes, the type of diet the dog has, exercise levels and whether the pet’s home has carpets or hardwood floors.

The latter is because carpets contain fire retardants, says Dr Promislow. ‘This has been suggested as a possible cause of disease such as cancer — but it’s hard to study the possible implications of these for human health because we are so long-lived.’

The team is investigating the feasibility of using high-tech dog tags ‘to collect information about the exact levels of these volatile compounds that both dogs and humans are exposed to in the home’, he adds.

The team also plan to check for other possible environmental risks, such as radon gas — a natural gas which increases levels of background radiation and has been linked to cancer. ‘We can compare dogs and see which get cancer and which don’t, and then go back to look at the environmental factors they may have been exposed to,’ he adds. ‘We are especially interested in finding out if there are risk factors in our environment that impact both humans and dogs.

‘If we find that there are certain diseases that tend to appear in dogs and their owners, this could indicate an environmental risk factor impacting both species.’

Most of the dogs will undergo an annual check-up at the vet to monitor their weight and general health. A proportion of the owners — around 4,000 so far — have also sent a swab taken from their dog’s cheek for the researchers to check their genetic profile. A smaller group will get a kit to take to the vet with samples of blood, urine, faecal matter and hair.

‘The hope is that we can identify biomarkers that allow us to predict or diagnose disease in dogs, and we hope these biomarkers might also be useful in humans,’ says Dr Promislow. More than 500 of the recruited dogs are being enrolled on a trial to test the drug rapamycin to extend lifespan.

This is a well-established anti-fungal agent, originally found in the bacteria of the soil of Easter Island off the coast of Chile.

Also known as sirolimus (and sold under brand names including Rapamune), it is already used in high doses in humans who have had a kidney transplant to stop the immune system mounting an attack on the donor organ, and to treat cancers, such as kidney cancer.

Animal studies have suggested it can also extend lifespan. Research published in 2009 in the journal Nature found that it could increase the lifespan of female mice by 14 per cent, and of male mice by 9 per cent.

Researchers at California University are now testing it on humans, recruiting 150 people aged 50 to 85 for a trial with a once-a-week low-dose (5mg) pill. The researchers will look at their bone mass, liver and kidney function and blood sugar levels, as well as other metrics, before and after taking the drug. Results are expected in 2023.

Rapamycin inhibits the action of mTOR, a protein found in the cells of humans and dogs. ‘mTOR is a central controlling hub that tells cells whether to grow or divide and also how to respond to damage and stress,’ says Professor Lynne Cox, head of the laboratory of ageing and cell senescence at Oxford University.

‘Genes are turned on or off by mTOR — it acts a bit like a tap. And what happens when you get older is that the tap is jammed on,’ she says. ‘Under those circumstances, mTOR doesn’t respond to signals coming in.’

This encourages chronic inflammation — ‘it’s like lighting lots of little fires around the body,’ says Professor Cox — and this is the basis for many diseases and age-related damage.

One of the things rapamycin does is turn down the chronic inflammatory state that goes along with ageing, ‘referred to as inflammaging’, says Dr Kaeberlein. Like Dr Promislow, he is a proud dog owner and says of his 11-year old German shepherd, Dobby: ‘I love him so much — and that makes this work personal to me. The science is important but it’s also important to have more time with our dogs, who are like family members.’

He explains that rapamycin is good at ‘knocking this chronic ageing back down to youthful levels and, as a result, it resets the immune system. When you can do that it has downstream consequences such as tissue regeneration and improvements to the microbiome [the community of bacteria that live in the gut and have a crucial role in the immune system].

‘It’s not a full rejuvenation — it’s resetting the clock a little bit. For example, if you take an old mouse and give it rapamycin, you see improvements in the oral cavity, the heart, the immune system. You can reverse periodontal disease within eight weeks. It’s an exciting molecule.’ The team has already run two small safety trials with rapamycin. In one, 24 middle-aged dogs were given rapamycin for ten weeks. Not only did it have no adverse effects but the dogs’ heart function improved, according to the results, published in the journal GeroScience in 2017.

The new trial will recruit dogs aged seven or older and weighing at least 40 lb, roughly labrador sized (as smaller dogs age less rapidly than bigger dogs — one of the aims of the Dog Aging Project is to find out why).

The dogs will be given one rapamycin tablet a week (wrapped in peanut butter or cheese) for a year and will be monitored up for two years after. (None of the team’s own dogs will take part in the project to avoid any conflict of interests.)

Professor Cox believes the trial could be ‘really significant’.

She says: ‘No one has ever done this size of trial [on rapamycin] in animals bigger than mice, and if you can show efficacy in dogs living with their owners then it makes a very strong case to go to the regulators and say “can we use this in humans this way, to modify ageing biology?”.

Rapamycin is licensed for use in humans with certain diseases and is off patent, so it’s relatively cheap.’ She is also ‘pretty confident’ that findings in dogs will apply to humans. ‘People differ a lot in their genes and in terms of lifestyle and environment, whereas lab mice are pretty much the same genetically and live in identical conditions,’ she says.

Pet dogs are more like humans in terms of their genetic and lifestyle differences, she says, ‘so the results stand a good chance of being relevant to humans’. However, she adds: ‘But we’d still need to conduct careful human trials.’

This isn’t the only area where pet dogs are advancing human health. In a recent study in Japan, pet dogs were given a drug for prostate cancer.

Dogs are one of the few animals with a ‘significant incidence’ of prostate cancer — and the pets in this trial had all developed the disease naturally.

Often for this sort of research, mice have to be genetically altered to develop the disease — but often, too, the outcomes in these rodents are not replicated in humans.

Researchers at Tokyo University gave the pets the immunotherapy drug mogamulizumab, which reduces levels of a type of white blood cell known as regulatory T-cells or Tregs.

These cells are thought to blind the immune system to the presence of prostate cancer cells. According to the results, published last month in the Journal for ImmunoTherapy of Cancer, the dogs given the drug had lower levels of Tregs and survived longer than those given a control. The drug will now be tested in humans.

But is data from pet studies reliable enough to lead the direction of treatment for humans? Dr Promislow admits one drawback is that, ‘dogs can’t tell us how they are feeling’.

And others have misgivings. Professor Richard Siow, director of ageing research at King’s College London, supports the focus of the Dog Aging project to improve healthspan.

‘As retirement age creeps up further, it is important that we can stay well for as long as possible,’ he says. ‘So research into approaches that may improve health span are more important than ever.’

And one big benefit of the Dog Aging Project is the sheer scale of it, he says. ‘They aim to study 100,000 dogs — it would be a hard to recruit that many humans.’

However, Professor Siow adds: ‘Dogs don’t have to worry about money or the daily commute. In short, they don’t experience stress in the way humans do. Stress causes inflammation, depression and less sleep — and plays a significant role in ageing.

‘Dogs are also often more healthy than humans — they have a controlled diet and are more physically active.

‘Having said that, there will be findings about biological processes that are important to humans, too.’

The early results of the lifestyle and diseases arm of the Dog Aging Project are expected later

this year — findings from the rapamycin study will take longer — but already trends are emerging.

For example, results published in November showed dogs that eat multiple times a day tend to be less healthy in terms of their bone and gut health, and had poorer cognition, than dogs fed once day — although Dr Promislow says that may be because they have underlying conditions that mean they need to be fed this way, like Frisbee.

However, rodents are often used for studying this kind of intermittent fasting, yet dogs, as large mammals that share our environment, offer a unique way to understand its effect in humans. Another benefit is that the research will look into diseases such as a form of bone cancer called osteosarcoma — which occurs in such small numbers in humans that it’s difficult to conduct meaningful research but is more common in dogs.

Dr Promislow describes the work of the Dog Aging Project as ‘an opportunity to learn about how we — dogs and owners — can spend more time together in better health’.

‘The dogs in this project are sentinels — like the canary in the coal mine. They will help us learn how to avoid what might make us age quicker but also inform us how to age better,’ he says.

Under the microscope

Singer Kiki Dee, 75, answers our health quiz

CAN YOU RUN UP THE STAIRS?

YES, but then I go to the gym twice a week. I mostly do aerobic exercises on the cross-trainer to help with my breathing — very important for a singer — and floor exercises for my stomach muscles. But I only do 40 minutes; otherwise I get bored.

EVER DIETED?

When I first moved to London from Bradford in my late teens in the 1960s, I got into the habit of binge eating. I’d alternate eating with starving. I was very weight-conscious because everyone was so slim and I was a bit podgy. Once I stopped bingeing, I cut out the usual suspects, such as carbs, and tried to eat smaller portions. Ironically, all these years later, I try to keep my weight up. When you get older, you don’t want to be too thin. I’m 5ft 6in and my ideal weight is 9st 1lb. I’m currently 8st 11lb, but I lost a lot of weight last year when my older sister, Betty, was dying.

ANY VICES?

I love a good trifle and I’ll have a doughnut once in a while.

HOW HAS THE PANDEMIC AFFECTED YOU?

I’m lucky as my acoustic guitarist collaborator Carmelo Luggeri has a sound studio in the village where we both live in Hertfordshire. So we spent much of lockdown writing a new album.

FAMILY AILMENTS?

We lost Betty, aged 76, to cancer and I was diagnosed with cancer of the neck of the womb when I was 40. I had radiotherapy for six months but it’s never returned.

POP ANY PILLS?

I’LL take vitamin C and zinc tablets during the winter because I don’t want to get a cough or cold.

TRIED ALTERNATIVE REMEDIES?

I did once try acupuncture when I was getting headaches in my 40s. It seemed to do the trick.

COPE WELL WITH PAIN?

Yes. I’m a pragmatic person. I just accept it and get on with it.

EVER HAD PLASTIC SURGERY?

I’ve never admitted to this before but, around ten years ago, I had my upper eyelids lifted. They were starting to ‘hood’, which was affecting my vision.

HAD ANYTHING REMOVED?

In my early 50s, I had my appendix out after suffering abdominal pains.

WHAT KEEPS YOU AWAKE?

As I’ve got older, I seem to let little things prey on my mind. I can get a bit wired, particularly if I’m going to be performing. So I practise meditation.

ANY PHOBIAS?

I’m not crazy about heights. We did some shows in Australia pre-Covid and there were some wonderful mountain-top views. But I wouldn’t go anywhere near the edge.

LIKE TO LIVE FOR EVER?

While I’m feeling this healthy, I want to carry on for as long as possible.

n The Long Ride Home by Kiki Dee and Carmelo Luggeri is out on April 22

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Read more at DailyMail.co.uk