Overview
- A Science paper published Thursday reports that the human hippocampus begins a coordinated structural and cellular shift in midlife based on single-cell and 3D-genome analyses of postmortem tissue.
- Researchers found that embryonically derived microglia, the brain’s resident immune cells, decline between about ages 50 and 75 and are replaced by cells with molecular signatures resembling peripheral blood immune cells and higher inflammatory activity.
- Cell populations that help maintain the blood–brain barrier declined with age, a change that could weaken vascular protection and let inflammatory molecules reach brain tissue.
- Across many hippocampal cell types the team observed a widespread erosion of three-dimensional genome architecture, meaning the physical folding and regulatory contacts of DNA degrade with age and link to shifts in gene regulation.
- The study analyzed 40 neurologically healthy adults and is cross-sectional so it shows association not causation; authors plan longitudinal and mechanistic follow-ups to test links to Alzheimer’s and to explore therapeutic strategies to preserve brain health.