Rebooting Immune Cells’ Metabolism Shields the Aging Brain in Mice

In an NIA-funded study, scientists discovered a process in which immune cells can drive aging in the brain. Their findings suggest that blocking this pathway may offer new ways to treat cognitive conditions such as Alzheimer’s disease.
As people age, they may have chronic low-level inflammation, which is linked to age-related diseases and cognitive decline. Normally, immune cells, including a group of cells called macrophages, help protect the brain. But as people — and mice — age, immune cells can start encouraging inflammation rather than protecting against it.

Researchers examined how a compound involved in regulating inflammation, called prostaglandin E2 (PGE2), affects macrophages and the aging process. When PGE2 was added to macrophages from both older mice and older humans in the lab, researchers found that PGE2 changed how the macrophages’ metabolism worked. Instead of producing energy, the macrophages stored their fuel and caused more inflammation. However, when the researchers added compounds that prevented the macrophages from taking in PGE2, the macrophages switched back to burning fuel.

Researchers then tested whether blocking the PGE2 pathway could help with cognition. The results suggest that maintaining macrophages’ normal metabolism can prevent aging-related cognitive decline in mice. Finding this new pathway could help researchers look for new treatments for aging-related problems with thinking and memory.
Visit the NIA website to read more about this research study.

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