S6K1 (Ribosomal protein S6 kinase 1)

S6K1 (ribosomal protein S6 kinase 1, encoded by RPS6KB1) is a serine/threonine kinase and a primary downstream effector of mTORC1 that promotes protein synthesis by phosphorylating ribosomal protein S6 and eIF4B, thereby stimulating ribosome biogenesis and translational capacity. It operates within a negative-feedback loop that attenuates insulin receptor substrate signalling, linking anabolic drive to insulin resistance. In model organisms from yeast to mice, genetic reduction of S6K1 activity extends lifespan and confers metabolic benefits, including improved insulin sensitivity and resistance to age-related adiposity; in humans, S6K1 hyperactivity is associated with obesity, type 2 diabetes, and accelerated cellular ageing, though direct longevity evidence in humans remains limited.