From Lab to Life: How Our Brains Age

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Science Daily reports that scientists have found three major changes that occur in our brains as we age, between 50 and 75.    It offers new clues to why aging sharply increases the risk of Alzheimer’s and other neurodegenerative diseases.

+ One of the biggest shifts occurred between about ages 50 and 75, when many of the brain’s original immune cells declined and were replaced by cells with more inflammatory characteristics.

+ Researchers also found weakening of cells that help maintain the blood-brain barrier,

+  ….along with widespread deterioration in the genome’s three-dimensional organization.

How did they discover this?  “…scientists used advanced single-cell methods to examine gene regulation and three-dimensional genome organization in individual cells from the human hippocampus, a brain region essential for learning and memory. By analyzing samples from adults across a wide range of ages, the team created one of the most detailed pictures yet of how genome regulation shifts as the brain grows older.”

“One of the most notable changes appeared in microglia, the immune cells that help maintain and protect the brain. Between approximately ages 50 and 75, the researchers found a sharp decline in microglia that originate during embryonic development. At the same time, those cells were increasingly replaced by cells whose molecular features resembled immune cells found in the blood.”

“Importantly, this study reveals that aging is not simply a gradual decline, but involves coordinated and dynamic remodeling of immune, vascular, and neuronal systems. These findings open the door to identifying new therapeutic targets aimed at preserving circuit integrity and brain function across the lifespan,” said Xiangmin Xu, PhD, Chancellor’s Professor and Director of the Center for Neural Circuit Mapping at the University of California, Irvine, and a co-corresponding author of the study.” **

** Nathan R. Zemke, Seoyeon Lee, Sainath Mamde, Bing Yang, Nicole Berchtold, B. Maximiliano Garduño, Hannah S. Indralingam, Weronika M. Bartosik, Pik Ki Lau, Keyi Dong, Emily Hsu, Amanda Yang, Yasmine Tani, Chumo Chen, Qiurui Zeng, Varun Ajith, Liqi Tong, Chanrung Seng, Daofeng Li, Ting Wang, Jingtian Zhou, Joseph R. Ecker, Christopher K. Glass, Carl W. Cotman, Xiangmin Xu, Bing Ren. Epigenetic and 3D genome reprogramming during the aging of the human hippocampus. Science, 2026; 393 (6809) DOI: 10.1126/science.adt8307