In 2009, a study found that rapamycin (sirolimus) could extend the lifespan of mice by 12%, and that those longer lives were also healthier. Dr. Dean Kellogg, Jr., PhD, thought, "This is too good to be true. A pill that can change aging and slow it down."
Mice aren't people, but Kellogg, a professor in the Department of Medicine, Division of Geriatrics, Gerontology and Palliative Medicine at UT Health San Antonio, was intrigued, and he has been studying rapamycin's potential to help humans ever since. For Kellogg, what caught his attention was that these mice not only had longer lifespans. They had longer healthspans.
“Healthspan is how long an organism can remain healthy and functional,” Kellogg explained. “You don't want to just hang around for another ten years in a nursing home being dependent on everything. You want to maintain your health so you can maintain independence, and that's what healthspan refers to.” Rapamycin appears to have the potential to help humans do that.
The drug seems to work by targeting the activity of a protein called mTOR—the "mechanistic Target of Rapamycin." Kellogg and his colleagues think the mTOR pathway plays a key role in improving the quality of a person's later years. The drug mimics the effects of calorie restriction, so the mTOR pathway starts seeking out alternative forms of fuel, like collagen. “In the mice studies, they found that it actually removed collagen from the great vessels. The aorta,” Kellogg said. “So that it basically reversed hardening of the arteries.”
There is no medication or supplement on the market today that can reverse hardening of the arteries. “So the result would be better blood flow to all the tissues, and you wouldn't be hammering on your brain blood vessels so hard,” Kellogg said, which could mean fewer strokes and better blood flow to the periphery. “You'd be rejuvenating, in many ways, your cardiovascular system,” Kellogg concluded.
A team of researchers at UT Health San Antonio, the academic health center of The University of Texas at San Antonio (UT San Antonio), has launched a multi-phase clinical study to better understand the biological effects of rapamycin in older adults. Kellogg said the purpose of the study is simple. “We're going to measure how effective rapamycin is in changing their mTOR activity from that of older persons to that of younger persons.”
In the first part of the study, researchers measured immune and metabolic markers in younger adults. This established a reference point for what optimal functioning looks like in healthy youth. As people age, the activity of the mTOR pathway increases and becomes dysregulated, so the second phase of the study involves testing doses of rapamycin in older adults to figure out how much might be enough to recreate the mTOR activity of a younger person.
Kellogg is looking for people between the ages of 65 and 90 to participate in this part of the study. It’s a six-week clinical trial in which every participant tests either rapamycin or another mTOR inhibitor called everolimus. After the six weeks are over, there is a four-month follow-up period.
“Rapamycin is safe, “ Kellogg stressed. “Whether it is effective for healthspan is yet to be proven, but the evidence favors that. This is the most promising, most scientifically backed age-ameliorating agent to date.”
If you are interested in participating in the study and are a non-smoker, between the ages of 65 and 90, who lives independently and does not have diabetes or use glucose-lowering medications, you can get more information by emailing BCRU@uthscsa.edu or calling (210) 450-3333.
Science & Medicine is a collaboration between TPR and The University of Texas Health Science Center at San Antonio, about how scientific discovery in San Antonio advances the way medicine is practiced everywhere.
