Added drug allows rapamycin to slow aging without risking diabetes
Laboratory mice that have received rapamycin have reduced the age-dependent decline in spontaneous activity, demonstrated more fitness, improved cognition and cardiovascular health, had less cancer, and lived substantially longer than mice fed a normal diet.
New research at the Linus Pauling Institute at Oregon State University suggests a fix for serious side effects of rapamycin*, a drug that appears to mimic the ability of dietary restriction to slow the aging process.
However, rapamycin has some drawbacks, including an increase in insulin resistance that could set the stage for diabetes, observed in both humans and laboratory animals. The new findings, published in the Journals of Gerontology: Biological Sciences, help to explain why that happens, and what could be done to address it.
It found that both dietary restriction and rapamycin inhibited lipid synthesis, but only dietary restriction increased the oxidation of those lipids in order to produce energy. Rapamycin, by contrast, allowed a buildup of fatty acids and eventually an increase in insulin resistance, which in humans can lead to diabetes.
However, the drug metformin can address that concern, and is already given to some diabetic patients to increase lipid oxidation. In lab tests, the combined use of rapamycin and metformin prevented the unwanted side effect.
“If proven true, then combined use of metformin and rapamycin for treating aging and age-associated diseases in humans may be possible,” the researchers wrote in their conclusion.
“This could be an important advance if it helps us find a way to gain the apparent benefits of rapamycin without increasing insulin resistance,” said Viviana Perez, an assistant professor in the Department of Biochemistry and Biophysics in the OSU College of Science.
“It could provide a way not only to increase lifespan but to address some age-related diseases and improve general health,” Perez said. “We might find a way for people not only to live longer, but to live better and with a higher quality of life.”