A previously unrecognized change in the brain’s immune system appears to emerge during middle age, offering new clues about how aging affects brain function and may increase vulnerability to neurodegenerative diseases.
The study, funded by the U.S. National Institutes of Health (NIH), found that significant changes in the population of immune cells in the hippocampus begin at around age 50. The hippocampus is a key brain region involved in learning and memory.
Microglia begin to change with age
The research focuses on microglia, specialized immune cells that play a central role in protecting and maintaining the brain. Scientists have traditionally believed that these cells, which are established during embryonic development, persist and renew themselves in the brain throughout life.
The new findings suggest that the picture may be considerably more complex.
Researchers from the University of California, San Diego, the New York Genome Center, and the University of California, Irvine, analyzed postmortem hippocampal tissue from 40 people between the ages of 20 and 95 who had no known neurological disorders.
The analysis revealed a gradual decline in the number of microglial cells between approximately ages 50 and 75. At the same time, cells displaying stronger inflammatory characteristics appeared to become more prominent. These cells share similarities with immune cells originating in the bloodstream.
The shift could provide new insight into why aging is so closely associated with chronic inflammation in the brain, a feature commonly observed in neurodegenerative disorders such as Alzheimer’s disease.
“Aging is the greatest risk factor for dementia, yet we still do not fully understand how it leads to disease,” said Richard Hodes, director of the U.S. National Institute on Aging.
Aging affects other brain cells too
The researchers examined not only which genes were active in the cells, but also their epigenetic signatures chemical changes that can provide information about a cell’s origin, condition, and history.
The study also found age-related deterioration in cells involved in maintaining the blood-brain barrier, the protective system that regulates which substances can pass from the bloodstream into the brain.
In addition, researchers observed widespread changes in the organization of genetic material across several different types of brain cells, suggesting that aging is accompanied by broader biological changes within the brain.
However, a key question remains unanswered: why do microglial cells gradually decline, and what role do the cells that appear to replace them play?
It is also not yet known whether this cellular shift directly contributes to the development of Alzheimer’s disease or other neurological disorders.
A new direction for aging research
A better understanding of how the brain’s immune environment changes during middle and later life could eventually open the door to new therapeutic strategies.
Researchers hope that such knowledge could help protect brain function, reduce chronic inflammation, and potentially make the aging brain less vulnerable to age related diseases.
The findings do not establish that this cellular transition causes dementia or Alzheimer’s disease. They do, however, add another important piece to the increasingly complex puzzle of how the human brain changes with age.