It was a bittersweet discovery: a drug that extends life but at the cost of causing diabetes. Now the drug's dual nature has been teased apart, raising the prospect of a new life-prolonging drug without the harmful side effects.
Rapamycin is regularly given to prevent transplant rejection and treat cancer. Previous studies have also shown that it extends the life of animals, but simultaneously causes glucose intolerance ? a side effect reported in humans, too.
David Sabatini of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and colleagues, gave the drug to strains of mice that had genes for certain proteins silenced. They found that rapamycin acts on two important nutrient-sensing proteins called MTORC1 and MTORC2. Its effect on the gene for MTORC1 prolongs life, while its action on MTORC2 causes diabetes.
Sabatini's team is now developing variants of rapamycin that act only on the gene for MTORC1. "If we could just target MTORC1, we could preserve longevity effects and get rid of the unwanted side effects," he says.
Journal reference: Science, DOI: 10.1126/science4.1215429
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