The study investigates the role of ribosomal protein S6 kinase 1 (S6K1) in regulating mammalian lifespan and age-related pathologies. In mice, deleting the *S6K1* gene led to an 80-day increase in median lifespan and improved resistance to age-related issues such as bone, immune, and motor dysfunction, as well as insulin resistance. The deletion of *S6K1* induced gene expression patterns similar to those seen in caloric restriction (CR) or pharmacological activation of adenosine monophosphate-activated protein kinase (AMPK). The findings suggest that S6K1 influences healthy mammalian lifespan and that therapeutic manipulation of S6K1 and AMPK could mimic the effects of CR, providing broad protection against aging-related diseases. The study also highlights the crosstalk between S6K1, AMPK, and other pathways, and the potential for developing drugs to manipulate these pathways to improve health in later life.The study investigates the role of ribosomal protein S6 kinase 1 (S6K1) in regulating mammalian lifespan and age-related pathologies. In mice, deleting the *S6K1* gene led to an 80-day increase in median lifespan and improved resistance to age-related issues such as bone, immune, and motor dysfunction, as well as insulin resistance. The deletion of *S6K1* induced gene expression patterns similar to those seen in caloric restriction (CR) or pharmacological activation of adenosine monophosphate-activated protein kinase (AMPK). The findings suggest that S6K1 influences healthy mammalian lifespan and that therapeutic manipulation of S6K1 and AMPK could mimic the effects of CR, providing broad protection against aging-related diseases. The study also highlights the crosstalk between S6K1, AMPK, and other pathways, and the potential for developing drugs to manipulate these pathways to improve health in later life.