Inflammation is a hallmark of brain aging, yet the source of inflammation in the old brain — and how to eliminate it — is still mysterious. This Innovation Grant project aims to manipulate inflammation in the aging brain as a potential avenue to promote brain resilience. The team will inject proteins that are engineered to have anti-inflammatory properties into old brains and test their impact on brain health using unbiased approaches at the single cell level. They will also develop new methods to promote the entry of these engineered proteins into the brain for potential therapeutic use. Finally, we will determine how immune cells infiltrate the old brain and if microbes such as bacteria or viruses are involved, with the goal of identifying ways to prevent this infiltration. By bringing together researchers with expertise in protein engineering, microbe analysis, and brain aging, this project has the potential to provide insight on how inflammation affects the aging brain and could lead to the generation of new therapies to promote brain resilience and counter dementias.