Neuroblast senescence in the aged brain augments natural kill cell cytotoxicity leading to impaired neurogenesis and cognition

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. Jin et al. discover the accumulation of natural killer (NK) cells in the aged brains of humans and mice. Neuroblast senescence in the dentate gyrus augments NK cell cytotoxicity that impairs neurogenesis and cognition during normal brain aging.

Automated summary

The accumulation of natural killer (NK) cells in the aging brain impairs neurogenesis and cognition, as neuroblast senescence in the dentate gyrus augments NK cell cytotoxicity during normal brain aging.