Drugs that can lengthen life have long been a hallmark of speculative science fiction – many hope for an invention that could extend average lifespans well into the triple digits in the distant future. But the timeline of these drugs could be shorter than we think. A new clinical trial published Wednesday in Science Translational Medicine has found evidence that low doses of two existing drugs can boost the immune system of an elderly person, helping it fight common deadly infections, including the flu, with seemingly little to no side effects.
The trial, run by scientists at the pharmaceutical company Novartis, involved more than 250 relatively healthy people over the age of 65 and was conducted from 2013 to 2015. The volunteers were randomly divided into five groups. Two groups received different doses of the approved chemotherapy and immunosuppressant drug everolimus; one received a dose of the experimental chemotherapy drug dactolisib; and one received a dose of everolimus and dactolisib combined (both drugs were developed by Novartis). The fifth group was simply given a placebo. The groups took the drugs or placebo daily for six weeks, then got the 2014 seasonal flu shot two weeks later. For the next nine months, their health was meticulously tracked though diaries and blood tests.
By the end of the year, all of the drug groups reported fewer infections than the placebo group. But the difference was largest among the people who took both drugs at once: They reported an average of 1.49 infections during the year, compared to the 2.41 infections reported by the placebo group. They were also the only treatment group whose blood showed a significantly better immune response to the flu vaccine to the placebo group, indicating they were more protected.
“This is an extremely important and exciting study,” Matt Kaeberlein, director of the Healthy Aging and Longevity Research Institute at the University of Washington, told The Guardian. Kaeberlein is unaffiliated with the research.
These drugs inhibit the production of mTOR, an enzyme that help cells produce other substances. For decades, though, scientists have suspected that mTOR plays a role in aging. Experiments in mice and other animals have shown that knocking out mTOR incidentally extends their lives. There are two major cellular pathways that mTOR is involved in, though, TORC1 and TORC2, and it’s only knocking out TORC1 that has been associated with anti-aging effects. In the low doses used by the researchers, the drugs only inhibit TORC1.
The effects of improved immunity seem to come without any major side effects. None of the treatment groups had a higher rate of side effects than the placebo group, and no single reported side effect, such as diarrhoea, was directly attributed to the drugs. There was even evidence that these drugs lowered the risk of high blood sugar and cholesterol as well as improved immune function.
“Available data indicates that mTOR antagonists are just as safe in geriatric persons as in transplant patients, thus mTOR antagonists are the leading candidates to be ‘anti-aging pills,’” Dean Kellogg Jr., a longevity researcher at the University of Texas Health Science Center at San Antonio, told Gizmodo via email. Kellogg Jr, unaffiliated with the current research, is conducting his own anti-aging trial of another mTOR drug.
“More studies to query the benefits of mTOR antagonists in ‘healthy older persons’ are needed... and the sooner the better,” he added.
That said, some caution is warranted. The study was only a Phase 2a clinical trial, which is used to figure out the best dosage of an experimental treatment. The next step is to suss out just how effective these drugs can be with a larger group of volunteers, and whether they can work better for vulnerable groups, such as the especially elderly (over age 85), who are at higher risk of dying from respiratory infections.
“Our clinical trial is a first step in determining if mTOR inhibitors can be used to promote healthy aging in humans,” study author Joan Mannick told Gizmodo. “However we still have a lot to learn, and the results need to be reproduced and validated in additional clinical trials.”
Though the current trial was conducted under the banner of Novartis, the company has since sold the licensing rights to everolimus and dactolisib (licensed under a different name) to be used as anti-aging treatments to the research company resTORbio. The company, co-founded by Mannick, is spearheading a Phase 2b clinical trial of these TOR inhibitors, set to be concluded by the end of the year. [Science Translational Medicine via The Guardian]
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