One of the body’s most important protective functions is the brain barrier system, including the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier. These barriers are made of highly specialized cells that fight off dangerous toxins and pathogens that may circulate in your bloodstream while allowing essential nutrients to enter. Scientists have long known what these barriers do, but less was known about how they are constructed during development.
Led by researchers at the University of California, San Diego, cell found senescent cells to be a major contributor. These cells, which are often associated with aging and disease, instead appear to help build and support the developing brain’s protective barrier.
At the heart of their new insights is an evolving understanding of senescent cells. Senescent cells have traditionally been called “zombie” cells because they are unable to divide but do not die completely. Senescent cells accumulate with age and are associated with tissue dysfunction, chronic inflammation, and cognitive decline, making them an attractive target for treatments aimed at slowing age-related decline.
However, new research in recent years has shown that senescent cells are not strictly linked to aging or disease. Researchers have identified senescent cells that appear temporarily during mouse fetal development and play a role in the development of limbs and kidneys. Other studies have found that senescent cells play a temporary role in wound healing, suggesting that these cells may be beneficial in some situations. This has led to the idea that aging is beneficial when it is temporary, but harmful when it persists.
Research from Associate Professor Hirui Mehalena’s lab in the School of Biological Sciences shows that senescent cells play a previously unrecognized role in brain development.
Studying the developing brains of mice, Associate Project Scientist Ashley Watson identified senescent cells that emerge at different stages during the formation of two important brain barrier systems: the blood-brain barrier and the blood-cerebrospinal fluid barrier.
We found that these age-related conditions appear in very specific types of barrier cells at precise moments in brain development, suggesting that they may play a specialized role in building the brain’s protective barrier. ”
Ashley Watson, Associate Project Scientist, University of California, San Diego
The researchers used an array of methods during their study, including single-cell RNA sequencing, imaging, and genetic lineage tracing. They found that three types of cells enter a senescent state during development: vascular endothelial cells, brain-resident macrophages, and choroid plexus epithelial cells. These cells contribute to the formation of the brain’s protective barrier in a variety of ways. In endothelial cells and macrophages, aging appears to help coordinate vascular patterning and blood-brain barrier formation. In the choroid plexus, which produces CSF and forms the blood-CSF barrier, aging appears to support barrier development and function.
They found that senescent vascular endothelial cells and brain-resident macrophages only appear transiently during the growth and remodeling of fetal blood vessels that form the blood-brain barrier. In contrast, choroid plexus epithelial cells retained their senescent features long after development and continued to exist into adulthood.
“This was one of the most unexpected discoveries,” Meharena said. “Developmental aging has generally been thought to be a transient process. Here, we have identified cell populations in the brain that appear to maintain aging-related characteristics into adulthood. This study shows that aging can take different forms in the brain, depending on cell type and developmental stage.”
To test whether these cells are functionally important, the researchers removed senescent cells during embryonic development. Mouse embryos lacking these cells have abnormalities in brain barrier formation and body fluid balance, indicating that aging-related cells contribute to normal brain development.
“What surprised us most was that aging is not a single condition. It looked very different in different cell types and seemed to perform different functions depending on where and when it occurred,” Watson said. “Moreover, the cells were not functioning independently. Aging appears to help different cell types work together to build and, in some cases, maintain the brain’s protective barrier.”
Researchers are currently studying how aging and related processes play out in brain diseases.
sauce:
University of California, San Diego
Reference magazines:
Watson, Louisiana; others. (2026) Persistent and transient senescent cells contribute to brain barrier development. cell. DOI: 10.1016/j.cell.2026.05.022. https://www.cell.com/cell/fulltext/S0092-8674(26)00581-7?_returnURL=.
