Cell Senescence as a Mediator of Age-Dependent Brain Inflammation
Innovation in Aging(2021)
摘要
Abstract Cellular senescence and inflammation are interconnected causes and consequences of tissue aging. Here, we implemented orthogonal approaches to study their interaction in steady-state mature and aged mouse brain. Using single cell sequencing, we identified a putative senescent microglial population, which increased in abundance with age and was characterized by increased expression of p16 and chemotactic senescence associated secretory phenotype (SASP) factors. Using p16-INK-ATTAC transgenic mice to eliminate p16ink4a-positive senescent cells and mass cytometry, we show that p16ink4a-positive cell targeting reduced the abundance of activated inflammatory cells in the aged female brain. Age-dependent declines in executive cognitive function were improved following transgenic p16ink4a-positive cell targeting, and executive function robustly correlated with inflammatory brain cell composition in females. Collectively, our findings demonstrate fundamental differences in the age- and sex-dependent brain inflammatory landscape and implicate p16ink4a-positive senescent cell targeting as a therapeutic strategy to attenuate age-related inflammation and cognitive decline.
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关键词
inflammation,cell,brain,age-dependent
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