Study demonstrates Resveratrol's ability to mitigate Alzheimer's Disease (AD) symptoms by inhibiting proinflammatory responses and promoting antioxidant enzyme expression in microglial cell lines, offering insights into its neuroprotective mechanisms.
Senescent microglia are a distinct microglial phenotype present in aging brain that have been implicated in the progression of aging and age-related neurodegenerative diseases. However, the specific mechanisms that trigger microglial senescence are largely unknown. Quinolinic acid (QA) is a cytotoxic metabolite produced upon abnormal activation of microglia. Brain aging and age-related neurodegenerative diseases have an elevated concentration of QA. In the present study, we investigated whether QA promotes aging and aging-related phenotypes in microglia and C. elegans. Here, we demonstrate for the first time that QA, secreted by abnormal microglial stimulation, induces impaired mitophagy by inhibiting mitolysosome formation and consequently promotes the accumulation of damaged mitochondria due to reduced mitochondrial turnover in microglial cells. Defective mitophagy caused by QA drives microglial senescence and poor healthspan in C. elegans. Moreover, oxidative stress can mediate QA-induced mitophagy impairment and senescence in microglial cells. Importantly, we found that restoration of mitophagy by mitophagy inducer, urolithin A, prevents microglial senescence and improves healthspan in C. elegans by promoting mitolysosome formation and rescuing mitochondrial turnover inhibited by QA. Thus, our study indicates that mitolysosome formation impaired by QA is a significant aetiology underlying aging-associated changes. QA-induced mitophagy impairment plays a critical role in neuroinflammation and age-related diseases. Further, our study suggests that mitophagy inducers such as urolithin A may offer a promising anti-aging strategy for the prevention and treatment of neuroinflammation-associated brain aging diseases.
Researchers at the Del Monte Institute for Neuroscience at the University of Rochester find that microglia-;the brain's immune cells-;can trigger cognitive deficits after radiation exposure and may be a key target for preventing these symptoms.
A study by Brigham investigators revealed how genetic changes in certain types of brain cells may contribute to the inflammatory response seen in Alzheimer's disease.
Life expectancy and healthy aging in mice can be determined by a protein present in some cells of the immune system, according to a study published in the journal Cell Reports.
Cleveland Clinic researchers analyzed genes and brain tissue of patients with Alzheimer's and found that differences in brain immunometabolism – the interactions between the immune system and the ways cells create energy – may contribute to women's increased risk for the disease and its severity.