Scientists are targeting a new set of recruits to test anti-ageing drugs: pet dogs. And according to their plans, not any old pooch will do. The researchers want to concentrate their trials on large canines. Golden retrievers, labradors and German shepherd dogs will do nicely.
The researchers are particularly interested in using pet dogs to test rapamycin. Developed as an anti-rejection drug for patients who have just undergone kidney transplants, rapamycin has recently been shown to extend the lives of mice by more than 10%.
Since this discovery was made in 2009, researchers have started projects aimed at establishing trials on humans to see if the drug could have a similar impact on men and women by protecting them against diseases of old age such as cancer and heart conditions. However, they acknowledge these could take many years to set up, gain ethical approval and then produce results.
“If you give rapamycin to 20-month-old mice – when they are in their equivalent of our middle age – you can see pretty profound benefits in terms of rejuvenating their bodies and increasing their lifespans,” said Dr Matt Kaeberlein, of the University of Washington in Seattle. “That is why we are so excited about the drug.
“The crucial point is that at that age, a mouse is the equivalent age of a nine-year-old dog. So if we now start giving the drug to middle-aged dogs, we have a chance of finding out in only a few years that it works on larger animals. The equivalent for that age for humans is 60. However, it will take much longer to obtain results from humans to see if the drug is working or not.”
The fact that pet dogs experience some of the same environmental influences as their owners is also helpful, he added. “We are doing this research to try to help dogs but we are well aware that what we learn could point the way to using rapamycin on humans. So anything we learn about other factors that influence the drug’s usefulness is going to be important.”
A successful outcome to dog trials would be twofold, added Kaeberlein. It would show that rapamycin could be added to pet food in order to extend the lives of household dogs. In addition, it would provide support for pressing ahead with trials of rapamycin on human volunteers. The dog trials would also provide key data on dosage and other parameters when designing trials using men and women as subjects.
Rapamycin acts on a protein that is involved in cell growth and has an anti-inflammatory impact on the body. It was also the first drug shown to extend lifespan in a mammalian species.
“As organisms age, inflammation can increase and that is related to many disorders,” added Kaeberlein. “But that is not the only thing that rapamycin does. It also turns on a process called autophagy which is in effect the process by which cells dispose of the garbage that builds up inside them.”
As animals get older, that cellular process declines in efficiency. Rapamycin gives autophagy a boost and restores its function. “It helps clear out the rubbish in our cells,” said Kaeberlein.
However, the drug – which is no longer protected by patent – is also associated with some severe side-effects. These include diabetes-like symptoms and complications of the lung. “These side-effects usually only occur when people take high doses of rapamycin during transplant surgery,” said Kaeberlein. “The key point about the trial that we are planning is that we will use only very low doses of rapamycin which will be added to the dogs’ food over long periods, probably years.”
For their research, Kaeberlein and his colleague Daniel Promislow are preparing to use a few dozen dogs in a trial that they hope will begin some time next year. As to the dogs selected, the team are looking for “mid to large” dogs, they say. “These dogs tend to have lifespans of 11 to 12 years and also tend to get heart disease and cancer,” said Kaeberlein. “These are conditions that rapamycin appears to be able to help ward off, so that makes them better subjects for our proposed trials.”
This makes dogs such as the golden retriever, labrador and German shepherd – aged around eight or nine years – perfect. “These are not laboratory trials,” Kaeberlein insists. “We are not going to do anything to the dogs once we have finished. We are just asking owners to cooperate with us to see if this drug, added to their pets’ diets, extends their lives significantly from middle age into senility.”
Kaeberlein said once their first trial has been completed, a larger study using hundreds of dogs could be set up in a few years. “That should be the one that really shows whether or not this drug will lengthen life – for dogs, and possibly humans.”
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