4.2 Pre-clinical studies of rapamycin in anti-aging
Rapamycin has been found to extend lifespan in diverse model organisms, including yeast, fruit flies, and nematodes 146-148 . Thus, studies have suggested that treating yeast with rapamycin, although making them smaller, can extend their longevity in a process that has been postulated to mimic caloric restriction149. Similarly, a landmark study by Harrison et al. revealed that rapamycin extends longevity in mammals150. They found that when treating genetically heterogeneous mice beginning at the age of 20 months with a daily dosage of 2.24 milligrams per kilogram of body weight, rapamycin can extend the lifespan of male mice by 9% and lifespan of female mice by 14%150. Remarkably, when increasing the dosage of rapamycin 3-fold compared to the previous study, the lifespan of mice was increased by up to 26% in female mice 151. Moreover, rapamycin has also been demonstrated to have protective effects against aging, which has been demonstrated in a high-profile study, the Intervention Testing Program (ITP) 152. This study used genetically outbred mice to test the potential of multiple anti-aging manipulations, including drugs, diets, and other interventions 153. Surprisingly, rapamycin is one of the only two drugs (the other is acarbose) that had robust anti-aging effect in the ITP experimental animal models.