Dietary supplementation of clinically utilized PI3K p110α inhibitor extends the lifespan of male and female mice

Abstract

Diminished insulin and insulin-like growth factor-1 signaling extends the lifespan of invertebrates1–4; however, whether it is a feasible longevity target in mammals is less clear5–12. Clinically utilized therapeutics that target this pathway, such as small-molecule inhibitors of phosphoinositide 3-kinase p110α (PI3Ki), provide a translatable approach to studying the impact of these pathways on aging. Here, we provide evidence that dietary supplementation with the PI3Ki alpelisib from middle age extends the median and maximal lifespan of mice, an effect that was more pronounced in females. While long-term PI3Ki treatment was well tolerated and led to greater strength and balance, negative im..