Strong inhibition of insulin/IGF-1 signaling in early-mid adulthood compresses morbidity, but in later life accelerates aging

) that is driven by healthspan expansion and compression of morbidity. Unexpectedly, cessation of DAF-2 AID in decrepit elderly individuals rejuvenates locomotory capacity and extends lifespan, showing that higher levels of IIS are optimal for health and survival towards the end of life. We also document a memory effect of transient IIS reduction during early adulthood, that is sufficient to fully extend lifespan (+189% median lifespan). Together, these findings demonstrate that both lifespan and healthspan can be maximized by appropriate temporal and directional modulation of IIS.