There's a new study underway to test whether it's possible to fend off age-related diseases with a novel combination of high-intensity interval training and anti-inflammatory medicines and supplements.
The small study includes healthy older adults, aged 65 to 80, who have agreed to try HIIT training, which includes short bursts of cardio, mixed with resistance training. In addition, all the participants will take daily capsules of spermidine, a supplement that is often marketed for healthy aging, as well as a generic medication that has potent anti-inflammatory effects.
"As we get older, the immune system is shifting away from good inflammation," which is the body's short-term, acute response to fend off injury or infection and promote healing, explains Dr. Thomas Marron, one of the researchers leading the new study. Marron directs early phase clinical trials at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
In contrast, pathogenic inflammation can stem from overactive immune cells releasing inflammatory signals after a prolonged response to a bacteria or virus. People also get chronic inflammation simply due to aging, which has been termed inflammaging. "It's not necessarily that we're getting more infections as we age, it's that we're getting more inflamed in general, as the immune system wanes. "It's this sort of bad inflammation that underlies the development of many different diseases," Marron says, everything from cancer, to heart disease to dementia.
"We hope that by decreasing this inflammation, we may be able to decrease the incidence of these diseases that become more common with age and we can promote more healthy aging," Marron says.
"I've reached the age where I worry about aging well," says study participant Robert Profusek, a lawyer in his 70s, who says he wants to stay as healthy and physically active as possible. "I don't want to get to a point where it takes me ten minutes to cross Park Avenue," he says.
After a few months of high-intensity interval training, or HIIT, mixed with resistance-band workouts, Profusek says he can feel the benefits. The workouts take him about 15 minutes a day, and include bouts of jumping jacks, aiming to do as many as possible in short bursts. "It's good for me," he says, noting that he's pushing himself.
He says he's under no illusion that he's guaranteed a long life, nor would he want to reach his 100th birthday if he wasn't in good health. "But the idea of slowing down aging, extending your runway, that's very attractive," Profusek says.
The goal of the research mirrors Profusek's wishes: to remain vital for longer. The research comes at a time when it's increasingly possible to make it to 100. By mid-century the number of centenarians in the U.S. is expected to quadruple to about 420,000.
Alongside this boom is an explosion of interest in anti-aging elixirs, everything from supplements, serums, injections and medicines. "You can get anything under the sun online," Marron says. "But it makes me very concerned when patients come in and they ask me, 'should I take this?' And I say, I have no idea. There's no science behind it."
The study underway now is a first step towards building the evidence for a combination of three interventions — each of which has shown some promise.
People who exercise regularly can reduce the risk of developing metabolic diseases, in part, due to the anti-inflammatory effects of exercise. And large observational studies have found that women who exercise and do strength training cut the risk of death from cardiovascular disease by 30%, compared to their less active peers.
Researchers chose to add the supplement spermidine to the mix, given research that shows spermidine can stimulate autophagy, which is the body's way of cleaning up damaged cells and reducing inflammation. Our bodies make spermidine naturally, but, as we age, production declines significantly, leading to lower levels. Spermidine supplements have been shown to extend lifespan in preliminary animal studies.
The study includes two types of generic medications. Half the participants will take lamivudine, which is an antiviral medication, and the other half of the participants will take rapamycin, which has long been prescribed to transplant patients to prevent organ rejection.
Both of these drugs have been FDA approved for decades to treat specific diseases. Now, the question is whether they will be effective in staving off age-related disease in healthy older people by tamping down inflammation.
Rapamycin has been a hot topic among longevity enthusiasts. "People have been taking it, off-label, at very low doses," Marron says. Taken in this way, the idea is that it can work as a powerful anti-inflammatory.
As with any medication or supplement, it's important to weigh risks and benefits. "There are a fair number of side effects that the patients can experience, and you don't really know which patients are going to get those," says researcher Philip Iffland of the University of Maryland who wrote a review of the pros and cons of rapamycin for longevity.
Marron's team will take blood samples from all the participants at multiple points throughout the year-long study, and they will analyze changes in markers of inflammation using a high-tech, high-resolution proteomic analysis. "We are running a test which looks at 5,300 different proteins, these are all cytokines and chemokines," Marron explains. These are signaling proteins that act like "traffic cops" for immune cells, coordinating the body's response to infection, injury and inflammation.
The analysis will help the researchers map all the proteins in the blood sample to find biomarkers and also provide a fuller picture of the immune response, showing how cells and proteins interact during acute or chronic inflammation.
The researchers hope to see a significant reduction in the 'bad inflammation' underlying all these diseases that come with aging, Marron says.
He and his team are now semi-finalists in the XPRIZE Healthspan competition. And, if their preliminary results are promising more research will follow. This summer, XPRIZE will announce 10 finalists to share a $10 million milestone prize and advance to the finals.
"We are thrilled by the powerful, innovative thinking and approaches we're seeing proposed by these teams," says Jamie Justice, Executive Vice President at XPRIZE Foundation and an adjunct professor at Wake Forest University School of Medicine. The goal of the competition is to have researchers develop interventions that can restore muscle, cognitive and immune function by a minimum of 10 years — with a goal of 20 years — and extend healthy life.
"It's a moonshot," says researcher Miriam Merad, Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, who is also leading the new study. "We hope to move the needle," she says, pointing to the importance of "laying the groundwork" for extending vitality, not just lifespan.
For Robert Profusek — who is taking part in the study — that's the point. "If you can do something like a regimen like this, to make your vitality extend," why wouldn't you, he says.
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