It was a discovery with a bitter aftertaste. Rapamycin prolongs life, but causes diabetes. Now that researchers have managed to separate these properties of this drug, a new life-extending drug is emerging without the harmful side effects.
Live longer, but with diabetes
Rapamycin (sirolimus) is usually given to prevent the patient's body from rejecting the donor organ after a transplant and as a therapy for cancer. Previous studies showed that rapamycin extends animal life (in mice) by around fourteen percent, but at the same time increases glucose intolerance - a side effect also reported in humans.
Action on two different proteins
David Sabatini of the Whitehead Institute for Miomedical Research in Cambridge, Massachusetts, and his colleagues gave the drug to genetically engineered mice with the genes for rapamycin's target proteins turned off. In doing so, they discovered that rapamycin responded to two important nutrient-responsive proteins, MTORC1 and MTORC2 (mammalian target Of rapamycin complex 1 and 2).
Rapamycin has been discovered in the soil bacteria Streptomyces hygroscopicus, a bacterium that occurs on Easter Island (Rapa Nui). The substance suppresses the immune system.
After the study, it became known that the action on the gene for MTORC1 prolongs life, while the action on the gene for MTORC2 causes diabetes.
Only life extension
Sabatini's team is now working on a form of rapamycin that only acts on MTORC1. If that succeeds, and the researchers can prevent their new variant from causing unpleasant effects elsewhere in the cell, a drug would be created that could effectively extend the lifespan by a number of years. If the effect would be as strong as in mice, it would be an average of ten years in humans. This comes at a price: even after elimination of glucose intolerance, suppression of the immune system means a reduced resistance, including against certain cancers. So don't cheer too soon.
The second step to a thousands of years old human dream: immortality, is getting closer. (The first step, discovering healthy living habits, is already commonplace). Incidentally, life extension in itself is not the most interesting goal. We have been living ten years longer than before the Second World War, but unfortunately the period without chronic diseases is just as long. The real challenge is to extend the time that people live without chronic disease, so that the quality of life improves significantly and it also becomes worthwhile to extend the time that we stay alive.
David M. Sabatini et al., Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity, Science (2012), DOI: 10.1126 / science.1215429 (paywall)
Pill against aging a step closer, Kennislink (2012)