Scientists find major brain shift between ages 50 and 75

September 15, 2026 at 07:31 PM1 min

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Researchers have found that the human brain undergoes broad changes in genome regulation starting in midlife, according to a study published in Science. The changes include a sharp decline in embryonic microglia and erosion of 3D genome architecture. The findings may help explain why age is the strongest risk factor for Alzheimer's disease.

Key Facts

The study was published in Science and used single-cell methods to examine gene regulation in the human hippocampus.
Between ages 50 and 75, embryonic microglia decline sharply and are replaced by blood-like immune cells with stronger inflammatory signatures.
The researchers observed a broad erosion of three-dimensional genome architecture across several brain cell types with age.
Bing Ren, PhD, is a corresponding author and Scientific Director and CEO of the New York Genome Center.

Microglial Shift

Between approximately ages 50 and 75, the researchers found a sharp decline in microglia that originate during embryonic development. Those cells were increasingly replaced by cells whose molecular features resembled immune cells found in the blood. The replacement microglia-like cells showed stronger inflammatory signatures, raising the possibility that they could contribute to chronic inflammation in the aging brain. Bing Ren, PhD, a corresponding author, said microglia are critical for maintaining brain homeostasis and that when they fail, toxic materials accumulate and may trigger inflammatory processes contributing to neurodegenerative diseases.

Genome Architecture Erosion

Across several types of brain cells, the researchers observed a broad erosion of three-dimensional genome architecture. Inside a cell, DNA is folded into a highly organized three-dimensional structure that helps control which genes are switched on or off. The researchers found that this organization became less orderly with age, suggesting that deterioration in genome structure could be a fundamental feature of brain aging. The researchers also detected a substantial decline in cell populations that help maintain the blood-brain barrier.