Breaking The Inflammatory Loop With Rapamycin

Originally derived from bacteria living on Easter Island, the drug Rapamycin has already displayed life extending properties in mice through affecting the mTOR pathway, which has since become a target of research. In a new development, intermittent dosing also appears to reduce inflammation and cancer in mice.

The discovery, published in Nature Cell Biology, showed that intermittent dosage of rapamycin can break the inflammatory cascade that follows cellular senescence; a particularly pressing problem after chemotherapy, which prevents division and triggers senescence. 

"DNA-damaging chemotherapy causes senescence, both to the tumor and its microenvironment. The tumor shrinks but the immediate tissue environment is inflamed. We think signals from those inflamed cells trigger residual cancer cells to grow again. In the mice, rapamycin suppressed the ability of the tumor cells to relapse."

After a burst of treatment, the inflammatory loop was somehow disrupted for a longer period of time, suggesting that rapamycin might be effective in intermittent treatment instead of continuous administration. This could help reduce some of the less desirable side effects like immunosuppression. 

 "It's an elegant solution - imagine using a small hammer to delicately knock out one thing that is causing problems. We knocked it out and it stayed out long enough to benefit the health of the animal."

The research may also help reveal more about rapamycin's life-extending properties, as this anti-inflammatory action may be an aspect of its benefit. Rapamycin is already of interest to anti-aging science and periodic dosage could prove equally beneficial, without carrying the risks of long term use. 

"We have yet to fully understand why suppressing the mTOR pathway via rapamycin increases lifespan and healthspan in mice. This work helps illuminates the puzzle," said Campisi. "Perhaps the mice are living longer because they have less overall inflammation, and maybe intermittent dosing will make it possible for us to use it more widely in humans."

Read more at Medical Express