Fountain Of Puppyhood: Can New Drug Lengthen Your Dog’s Life? 
 
 Can a drug that gave mice longer lives and improved brain function work for dogs and people too? A new study plans to find out. 
 
 By Vicki Croke 
 
 Given the opportunity, would you sign your beloved dog up for a drug trial that stood the chance of adding years to his or her life (but might also have some unknown side effects)? 
 
 That’s not a hypothetical question. Researchers at the University of Washington in Seattle have just proposed a trial in which an anti-aging drug will be given to pet dogs whose owners choose to participate. 
 
 The drug, rapamycin, which was originally developed as an anti-rejection drug for humans receiving kidney transplants, is pretty tempting. The substance is involved in cell growth, and, in animal trials, it’s been shown to increase the lifespan of female mice by 13 percent. 
 
 For those of us with large or giant breed dogs, longevity is an especially painful topic. Wolfhounds and great Danes are among the heartbreakers. 
 
 According to WebMD: 
 
 “All dog breeds are the same species, yet they age at very different rates,” says David Waters, DVM, PhD, professor and associate director of the Purdue University Center on Aging. “We still don’t understand why.” The rare Mexican breed, the Xoloitzcuintle, has a life span of 15 to 20 years, for example, while the Irish Wolfhound has an estimated 6 to 8 year life expectancy…. Nearly 40% of small breed dogs live longer than 10 years, but only 13% of giant breed dogs live that long. The average 50-pound dog will live 10 to 12 years. But giant breeds such as great Danes or deerhounds are elderly at 6 to 8 years. 
 
 And, indeed, rapamycin researchers are targeting specifically those dogs with shorter lifespans. 
 
 According to Nature News: 
 
 The researchers hope to test rapamycin in large dogs that typically live for eight to ten years; they would start giving the drug to animals aged six to nine. A pilot trial would involve about 30 dogs, half of which would receive the drug, and would allow the researchers to dose the dogs for a short time and observe effects on heart function and some other health measures. The trial could be completed in as little as three years, but researchers will know long before that — perhaps in months — whether rapamycin improves cardiac function or other aspects of health. Rapamycin acts on a protein that is involved in cell growth, but little is known about how it extends life. It might retard the ageing process itself or it might prevent age-related diseases. One hypothesis is that it works primarily by preventing the development of cancers. 
 
 The notion that this drug may slow down the aging process and/or prevent the development of cancer is exciting. And, rapamycin, which comes from isolated bacterial products in the soil of Easter Island, may also even boost cognitive function. But, of course, there are cautions. 
 
 Rapamycin has been linked to an increased risk of diabetes in humans who’ve had kidney transplants, and other side effects could emerge. 
 
 The purpose of the trial is to get a step closer to understanding how rapamycin might work as a fountain of youth for humans. So why not just try it on people? There are a few reasons. 
 
 According to the International Business Times: 
 
 The drug is no longer patentable so few companies would be willing to invest in it as an anti-ageing compound. Human trials are also extremely expensive and to test if it extends a person’s lifespan would take a very long time. 
 
 Dogs have become candidates because they share our lifestyles and some of our old-age diseases. 
 
 According to Nature News: 
 
 Pet dogs should provide a more realistic test than lab mice of how the drug would work in humans. Pets experience some of the same environmental influences and get some of the same age-related diseases as their masters, says [molecular biologist Matthew] Kaeberlein. (He plans to enroll his own German shepherd dog when it is old enough.) Other researchers say that Kaeberlein and [Daniel] Promislow’s reasoning makes sense. “We’re talking about whether aged pets will benefit, and that’s a good model for a human population,” says physiological geneticist David Harrison of the Jackson Laboratory in Bar Harbor, Maine, who has studied rapamycin in mice. 
 
 But before you answer the question of whether you’d sign your dog up for this study, it’s important to note that, as is standard, about half the dogs will receive not rapamycin, but a placebo. 
 
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 ||||| Timothy Clary/AFP/Getty Images 
 
 Yeast, worms and mice: all have lived longer when treated with various chemical compounds in laboratory tests. But many promising leads have failed when tried in humans. This week, researchers are proposing a different approach to animal testing of life-extending drugs: trials in pet dogs. Their target is rapamycin, which is used clinically as part of an anti-rejection drug cocktail after kidney transplants and which has also been shown to extend the lives of mice by 13% in females and 9% in males (D. E. Harrison et al. Nature 460, 392–395; 2009). 
 
 The compound’s effect on lifespan has not yet been tested in people — human trials are expensive and it takes a long time to learn whether a drug can extend a human life. Furthermore, rapamycin is no longer patentable, so pharmaceutical companies are unwilling to invest effort in it. The drug can also cause some serious side effects that might rule it out as a pharmaceutical fountain of youth. It has, for example, been linked to an increased risk of diabetes in people who have had kidney transplants (O. Johnston et al. J. Am. Soc. Nephrol. 19, 1411–1418; 2008). But at low doses, researchers suspect that the drug will not be a problem for healthy dogs. 
 
 “Any compound has side effects of some sort; the question is what kind of side effects one can live with,” says Randy Strong, a gerontologist at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. 
 
 To answer that question, molecular biologists Matthew Kaeberlein and Daniel Promislow at the University of Washington in Seattle propose to give low doses of rapamycin to dogs in a study that would also test whether the drug can extend the animals’ lives. The pair invited experts in canine health and the biology of ageing to a meeting in Seattle on 28–29 October to discuss how to structure such a trial. 
 
 The researchers hope to test rapamycin in large dogs that typically live for eight to ten years; they would start giving the drug to animals aged six to nine. A pilot trial would involve about 30 dogs, half of which would receive the drug, and would allow the researchers to dose the dogs for a short time and observe effects on heart function and some other health measures. The trial could be completed in as little as three years, but researchers will know long before that — perhaps in months — whether rapamycin improves cardiac function or other aspects of health. 
 
 Rapamycin acts on a protein that is involved in cell growth, but little is known about how it extends life. It might retard the ageing process itself or it might prevent age-related diseases. One hypothesis is that it works primarily by preventing the development of cancers. 
 
 Pet dogs should provide a more realistic test than lab mice of how the drug would work in humans. Pets experience some of the same environmental influences and get some of the same age-related diseases as their masters, says Kaeberlein. (He plans to enrol his own German shepherd dog when it is old enough.) 
 
 Other researchers say that Kaeberlein and Promislow’s reasoning makes sense. “We’re talking about whether aged pets will benefit, and that’s a good model for a human population,” says physiological geneticist David Harrison of the Jackson Laboratory in Bar Harbor, Maine, who has studied rapamycin in mice. 
 
 Kaeberlein and Promislow have collected about US$200,000 in University of Washington institutional funds for the pilot. But they will need much more funding for a larger trial of several hundred dogs to test whether the drug, given over years, can extend lifespan — and to study the normal ageing process in thousands of animals to try and understand the mechanism of any life-extending effects. 
 
 Participants at the Seattle meeting are also considering whether pet owners could be asked to help fund a bigger trial and if so, whether researchers could promise donors that their dogs would be treated with rapamycin rather than a placebo without compromising the study. Usually, participants in a gold-standard clinical trial are randomly assigned to a treatment or control group. 
 
 “It’s a kind of unique situation because they are people’s pets,” says Kaeberlein. “We haven’t come to any decision on how that’s going to be handled.”
– Testing potentially life-extending drugs on humans is neither a quick nor cheap undertaking, and researchers now want to turn to man's best friend for help. In the past, such drugs have been successful on worms and mice, but they've failed when it comes to humans, Nature reports. Dogs, however, suffer from some of the same age-related diseases we do, and they also live in comparable environments—meaning they could offer a better look at how the drugs might affect us. In this case, researchers want to test a drug called rapamycin, which comes from a chemical found in the soil of Easter Island, WBUR reports. Studies in mice have shown that it extends females' lives by 13% and males' by 9%. University of Washington in Seattle researchers are proposing a pilot trial composed of 30 large dogs aged six to nine whose lifespan is typically no more than 10 years; researchers would provide half of them with the drug. It's not entirely clear how rapamycin, which is used in people to prevent rejection after kidney transplants, contributes to a longer life; one theory is that it keeps cancer at bay. On the downside, it's been tied to a heightened risk of diabetes among the kidney-transplant patients who have taken it. (In other Easter Island news, scientists now believe the islanders weren't as isolated as long thought.)