U.S. Department of Health and Human Services

Molecular Insights Could Lead to New Drugs to Extend Healthy Lifespan

Researchers have identified a molecular mechanism that could spur the development of new drugs that may lengthen healthy lifespan. A few years ago, the drug rapamycin was found to extend the lifespan of mice. However, rapamycin treatment—though U.S. Food and Drug Administration-approved for use in preventing rejection of transplanted organs and other applications—also comes with significant side effects, including increased susceptibility to infection (because it suppresses the immune system), toxicity to certain organs, and—surprisingly—elevation of blood glucose levels, especially after meals. Rapamycin inhibits a protein called mTOR, which integrates signals from nutrients and growth factors. In new research, scientists sought to understand the molecular mechanisms by which rapamycin extends lifespan yet elevates blood glucose levels. They found that in mice, rapamycin reduced the activity of two different mTOR-containing protein complexes, designated mTORC1 and mTORC2. Using genetically engineered mice to tease out the effects of the different mTOR complexes, they found that the mechanisms by which rapamycin is affecting lifespan and glucose levels are independent: glucose elevation resulted from the mTORC2 inhibition, while the lifespan extension was an effect of inhibiting mTORC1. These findings may pave the way toward the development of new therapies to extend healthy lifespan by targeting mTORC1, while avoiding some of the unwanted side effects associated with rapamycin. 

Lamming DW, Ye L, Katajisto P, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335: 1638-1643, 2012.