IGF signaling controls aging and affects age-related neurological diseases. Specifically downregulating IGF pathways promotes longevity in mice through improvements of tissue homeostasis and cellular stress resistance. To investigate the long-term effects of IGF signaling on the physiological renewal of neurons in the aging brain, we genetically suppressed IGF1R in adult neural stem cells (NSC) and performed cell lineage tracing. We could show that IGF1R knockout maintained youthful characteristics of olfactory bulb (OB) neurogenesis within the aging brain. Counter-intuitively, blocking IGF signaling in NSCs increased the cumulative production of neuroblasts and enhanced the lifelong integration of new neurons into the OB. These neuro-anatomical changes improved olfaction and efficiently prevented age-related functional decline. Thus, inhibiting longevity gene IGF1R in adult NSCs optimized cell renewal during aging and enhanced sensory capacity. Interestingly, suppression of IGF signaling not only postpones cellular and organismal aging, but also has the potential to alleviate experimental neurodegeneration, in particular Alzheimer disease in mice: We showed recently that suppressing IGF signaling in adult neurons protects the brain from amyloid pathology. Mutants lacking neuronal IGF-1R exhibited improved memory, fewer plaques and diminished neuroinflammation. Neurons undergoing IGF1RKO reduce their apical soma and develop leaner dendrites, indicative of structural plasticity. Our data indicate that resistance of neurons to IGF protects lifelong from Alzheimer pathology through enhanced Aβ clearance, turning neuronal IGF receptors into a promising target for AD treatment. Functional analysis using microarray data comparing neurons in the early stages of AD with IGF1R KO neurons revealed strongly convergent signatures involving neurite growth, cytoskeleton organization, stress response and neurotransmission. We showed that neuronal defenses against AD rely on an endogenous gene expression signature similar to the neuroprotective response activated by genetic disruption of IGF1R. Collectively, these studies highlight neuronal IGF1R signaling as a relevant target for developing AD prevention and anti-aging strategies.