Rapamycin, an inhibitor of the mTOR pathway, extends the lifespan of genetically heterogeneous mice when administered starting at 600 days of age. The study, published in Nature, shows that rapamycin increases median and maximal lifespan in both male and female mice. Female mice showed a 14% increase in lifespan, while male mice showed a 9% increase. These results were consistent across three independent test sites, indicating that the effect is not genotype-specific. Rapamycin did not alter disease patterns in mice, suggesting that the extension of lifespan is not due to a reduction in strain-specific diseases. Rapamycin may extend lifespan by delaying death from cancer, retarding aging mechanisms, or both. This study is the first to demonstrate a role for mTOR signaling in regulating mammalian lifespan and pharmacological extension of lifespan in both genders. The findings have implications for the development of interventions targeting mTOR for the treatment and prevention of age-related diseases. The study used genetically heterogeneous mice, which are more representative of the human population. The mice were fed a diet containing rapamycin starting at 600 days of age, and their survival was monitored. The results showed that rapamycin-fed mice lived longer than control mice, with a significant increase in survival to the last decile, a measure of maximal lifespan. Rapamycin reduces the function of the TOR kinase and has anti-neoplastic activities. Genetic inhibition of TOR extends lifespan in short-lived model organisms. The study found that rapamycin-fed mice had extended median and maximum lifespan at all three test sites. The results were consistent across different sites and genders, with significant improvements in survival for both male and female mice. The study also found that rapamycin-fed mice had a higher 90th percentile survival age compared to control mice, indicating that rapamycin increases the age at which 90% of mice have died. The results suggest that rapamycin may extend lifespan by delaying aging processes and reducing the risk of death from cancer. The study provides evidence that mTOR signaling plays a role in regulating mammalian lifespan and highlights the potential of rapamycin as a therapeutic agent for age-related diseases.Rapamycin, an inhibitor of the mTOR pathway, extends the lifespan of genetically heterogeneous mice when administered starting at 600 days of age. The study, published in Nature, shows that rapamycin increases median and maximal lifespan in both male and female mice. Female mice showed a 14% increase in lifespan, while male mice showed a 9% increase. These results were consistent across three independent test sites, indicating that the effect is not genotype-specific. Rapamycin did not alter disease patterns in mice, suggesting that the extension of lifespan is not due to a reduction in strain-specific diseases. Rapamycin may extend lifespan by delaying death from cancer, retarding aging mechanisms, or both. This study is the first to demonstrate a role for mTOR signaling in regulating mammalian lifespan and pharmacological extension of lifespan in both genders. The findings have implications for the development of interventions targeting mTOR for the treatment and prevention of age-related diseases. The study used genetically heterogeneous mice, which are more representative of the human population. The mice were fed a diet containing rapamycin starting at 600 days of age, and their survival was monitored. The results showed that rapamycin-fed mice lived longer than control mice, with a significant increase in survival to the last decile, a measure of maximal lifespan. Rapamycin reduces the function of the TOR kinase and has anti-neoplastic activities. Genetic inhibition of TOR extends lifespan in short-lived model organisms. The study found that rapamycin-fed mice had extended median and maximum lifespan at all three test sites. The results were consistent across different sites and genders, with significant improvements in survival for both male and female mice. The study also found that rapamycin-fed mice had a higher 90th percentile survival age compared to control mice, indicating that rapamycin increases the age at which 90% of mice have died. The results suggest that rapamycin may extend lifespan by delaying aging processes and reducing the risk of death from cancer. The study provides evidence that mTOR signaling plays a role in regulating mammalian lifespan and highlights the potential of rapamycin as a therapeutic agent for age-related diseases.