A synthetic biology platform to identify novel anti-aging natural products

DESCRIPTION (provided by applicant): The ultimate goal of research into the biology of aging is to identify pharmaceutical interventions to increase both lifespan and healthspan of humans. The natural product rapamycin has been shown to significantly extend the lifespans of all model organisms tested including fungi, flies, worms, and mice. However, chronic treatment with rapamycin also causes unwanted side effects including moderate immunosuppression and impaired glucose tolerance and insulin function. Recent research suggests that rapamycin functions by binding and blocking signaling from two independent signaling complexes, mTORC1 and mTORC2. It has been shown that the beneficial effects on lifespan are due to the downregulation of mTORC1 signaling upon binding by rapamycin. On the other hand, the deleterious side effects of rapamycin result from the downregulation of mTORC2 signaling upon rapamycin binding. Thus, an ideal anti-aging pharmaceutical agent would be highly similar to rapamycin, but have