Austad has been examining the effects of known pharmaceuticals on slowing the aging process, mostly in mice. “We found a drug where, not only do the mice live longer, but it also improved many aspects of their health,” he says.
The news gets better. The drug has been in use with some of the most vulnerable sectors of the population. “Rapamycin not only exists in use in human medicine, but it’s only given to people who are really, really sick,” Austad says.
Currently, rapamycin makes up part of a cocktail of medicines used to suppress the immune system after kidney transplants. In cardiac patients, it coats stents to stop cells from dividing and causing scarring and blockages.
“Aging is the number one cause of death,” Austad says. “All the top causes of death increase by dozens, even hundreds, of folds when you get older. So getting older is a key feature of all these diseases.” Therefore Austad is seeking to treat the underlying cause of aging to delay the onset and progression of all these diseases at the same time.
So far, research on mice shows that rapamycin prevents or delays some types of cancer and heart aging, enhances resistance to pneumonia, reduces anxiety and depression, and slows normal brain aging, all while delaying the onset of Alzheimer’s disease.
“Then we thought about how this drug is used now to suppress the immune system,” Austad says. “So maybe it affects all these diseases, which is good, but what if the first time you get the flu, you die. That’s a big problem.”
So they gave mice the drug and then introduced the bacteria that produces pneumonia. “The mice with the rapamycin actually did better than those without,” Austad says. The rapamycin-dosed mice that were introduced to the flu did not fare any better or worse than their drug-free counterparts. That put the immune-deficiency fears to rest.
In fact, rapamycin actually proved to boost the efficacy of flu vaccinations if given in advance of the injection. “Every year, you get your flu vaccine, and what they don’t tell you, is that the vaccine is much less likely to provide impact on the elderly because it relies on the immune system responding to the vaccine,” Austad says.
Researchers gave one group of mice rapamycin, along with a control group that did not receive rapamycin, and then injected a flu virus in both groups. 80 percent of mice without the drug died. No mice died who had been given rapamycin.
Despite the drug being widely used now in humans, Austad says it is not ready to be prescribed for anti-aging purposes. “We have not even found the best dosage in mice, and we need to test it in other animals to look for side effects,” he says.
With such potent benefits, pharmaceutical companies are forging ahead with their own trials. But they tweak the cheap, generic version enough to lock in new patent rights. One study done with humans by Novartis has already found the same overall benefits.
Other drugs are also testing well for anti-aging properties, though none can measure up to rapamycin so far. Rapamycin increases longevity 10 to 25 percent. Female mice gained a slightly greater effect than males. “That was totally unexpected,” Austad says. “We don’t think about giving medicines to women or men based on their sex. But if men could stay alive as long as women, and women could stay as healthy as men, we’d both be better off.”
In another drug, acarbose, usually prescribed for type 2 diabetes, male mice lived 22 percent longer with females only faring better by five percent. “Nobody understands that at all,” Austad says.
The confusion is not surprising considering that gender as a factor in animal testing is relatively new. The National Institutes for Health did not require both sexes in testing until last year. Up to then, the studies were done almost exclusively on males. The rationale was that the hormonal fluctuations from the female reproductive cycles would create too many variables.
Newer to the anti-aging testing arena, acarbose lags far behind rapamycin in studies. Varied-dosage testing could reveal far greater effectiveness in the future, but that takes time.
A drug called metformin, also used to treat type 2 diabetes, has not been nearly as effective in mice, but does have a long history of human use. “So it’s not as big of an effect on aging, but it’s unlikely to have side effects,” Austad says.
A natural substance used in Native American medicine and derived from the creosote bush, called nordihydroguaiaretic acid or NDGA, has potential, but only for males.
Austad expects clinical trials on rapamycin with humans to begin within two to three years. “The exciting point is that we have all these results,” he says. “It’s not pie in the sky. It’s in our future.”
