A drug that eliminates senescent cells damaged healthy neurons in culture; Julie Andersen’s group is developing targeted immune cells for the brain
A drug that eliminates senescent cells damaged healthy neurons in culture; Julie Andersen’s group is developing targeted immune cells for the brain
In an interview with Modern Healthspan on October 15, Julie Andersen, a professor at the Buck Institute for Research on Aging, linked mitochondrial damage to inflammation in the brain. Her laboratory is studying two approaches: reducing inflammatory signaling in senescent cells and directing an immune cell to release a therapeutic protein near amyloid deposits.
Mitochondria supply cells with energy and contain their own DNA. When a damaged mitochondrion releases DNA fragments into the cytoplasm, the cell’s internal environment, the sensor protein cGAS detects them. The protein STING then activates inflammatory genes. In Andersen’s model, inflammation and mitochondrial damage can reinforce each other in neurons and glia, the brain’s supporting and immune cells.
In a mixed culture of human neurons and glia, navitoclax, a drug that eliminates senescent cells, killed healthy neurons at a dose that eliminated senescent astrocytes. Andersen’s group is developing a preclinical system using genetically modified regulatory T cells, immune cells that suppress inflammation. The intended design would allow a cell to enter the brain, recognize an amyloid deposit, an accumulation of protein between nerve cells, and release a selected protein nearby: an anti-inflammatory factor, a growth factor, an antibody, or a protein that eliminates senescent cells.
In cell experiments, genetically modified mouse fibroblasts recognized β-amyloid, while mouse T cells recognized β-amyloid and tau protein. These experiments test target recognition and response activation, the functions the targeted cell would need to perform.
In a separate experiment in human fibroblasts, cells found in connective tissue, urolithin A reduced the amount of DNA in the cytoplasm, cGAS–STING activity, and the release of inflammatory factors. Senescence had been induced by chemotherapy or repeated cell division; the cells remained viable after treatment.