# NIH-funded study finds hippocampal microglia shift starting around age 50

_Tuesday, August 4, 2026 at 8:41 PM EDT · Science · Latest · Tier 2 — Notable_

NIH-supported research reports that the immune cell population inside the human hippocampus undergoes a major transformation beginning in middle age, a change that may contribute to cognitive decline and dementia risk later in life, SciTechDaily reported.

Researchers from the University of California, San Diego, the New York Genome Center and the University of California, Irvine used single-cell methods on postmortem hippocampal tissue from 40 neurologically healthy adults aged 20 to 95. Their analysis suggests microglia, the brain's main resident immune cells, steadily decrease from about age 50 to 75, while cells with stronger inflammatory signatures and features resembling peripheral blood-derived immune cells take their place.

The finding challenges the assumption that microglia that develop in embryonic life continually renew themselves and remain in the brain throughout life. First author Nathan Zemke of UC San Diego said combining gene expression with 3D genome and epigenome mapping uncovered a shift in immune cell identity and lineage that expression data alone would not have revealed.

NIA director Richard Hodes said aging is the largest risk factor for dementia and that the microglial shift may help explain how aging drives disease. The study on epigenetic and 3D genome reprogramming during aging of the human hippocampus was published in Science with DOI: 10.1126/science.adt8307, supported by NIA grants and the NIH Common Fund 4D Nucleome program.

## Sources

- [SciTechDaily](https://scitechdaily.com/scientists-discover-a-major-brain-change-that-starts-around-age-50/)

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