Cellular Senescence Halted to Curb Neuroinflammation

PNAS Nexus

A study in mice suggests that senescent cells are at least partially responsible for post-surgical delirium and similar conditions in elderly people—and identifies a combination of drugs that might be able to prevent the complication.

Elderly people sometimes experience neurocognitive problems after infections or surgeries. Shyni Varghese and colleagues investigated the role of cellular senescence in the neuroinflammation that occurs in these cases. Cellular senescence is a normal process that helps prevent abnormal cell proliferation, but it can also occur in response to stress. Senescent cells stop dividing and typically secrete pro-inflammatory cytokines and other molecules that can enter the brain and induce senescence in nearby brain cells. Cellular senescence has been linked to age-related neurodegenerative conditions, including Alzheimer's disease. The authors measured changes in aged mice before and after tibial fracture surgery, finding that surgery resulted in significant accumulation of senescent cells in the hippocampal region of aged mice. The authors also dosed some mice with a combination of Dasatinib and Quercetin that has been shown to reduce senescent cells. Treated mice showed a significant reduction in surgery-induced neuroinflammation compared to untreated mice. According to the authors, the findings have implications for the development of new therapies for neuroinflammation and post-surgery delirium in particular.

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