Normal aging is accompanied by escalating systemic inflammation. Yet the potential impact of immune homeostasis on neurogenesis and cognitive decline during brain aging have not been previously addressed. Here we report that natural killer (NK) cells of the innate immune system reside in the dentate gyrus neurogenic niche of aged brains in humans and mice. In situ expansion of these cells contributes to their abundance, which dramatically exceeds that of other immune subsets. Neuroblasts within the aged dentate gyrus display a senescence-associated secretory phenotype and reinforce NK cell activities and surveillance functions, which result in NK cell elimination of aged neuroblasts. Genetic or antibody-mediated depletion of NK cells leads to sustained improvements in neurogenesis and cognitive function during normal aging. These results demonstrate that NK cell accumulation in the aging brain impairs neurogenesis, which may serve as a therapeutic target to improve cognition in the aged population.

正常衰老伴随着不断升级的全身炎症。然而，免疫稳态对大脑衰老过程中神经发生和认知能力下降的潜在影响之前尚未得到解决。在这里，我们报告先天免疫系统的自然杀伤 (NK) 细胞存在于人类和小鼠老年大脑的齿状回神经源性生态位中。这些细胞的原位扩增有助于它们的丰度，这大大超过了其他免疫亚群。老化齿状回内的神经母细胞显示出与衰老相关的分泌表型，并增强 NK 细胞活动和监视功能，从而导致 NK 细胞消除老化的神经母细胞。NK细胞的遗传或抗体介导的消耗导致正常衰老期间神经发生和认知功能的持续改善。