Microglial Cells Show Sex-Based Distinctions in Aging, Contributing to Cognitive Decline

Microglial Cells Show Sex-Based Distinctions in Aging, Contributing to Cognitive Decline

Microglial cells are essential for maintaining brain health and function by protecting against pathogens and pruning damaged neurons. However, the aging process can affect the functionality of these cells, potentially leading to cognitive decline and brain dysfunction. A recent study led by researchers at Fudan University aimed to unravel the mechanism of microglial cell aging and its impact on the brain.

The study, conducted using male and female mice, revealed surprising sex-based distinctions in microglial aging. The researchers found that aged-like microglia contributed to cognitive decline even in young mice. They developed a method called 3xDR, which allowed them to study aged microglial cells in young brains and examine their role in cognitive decline and myelin impairment.

By profiling the transcriptomes of microglial cells in both male and female mice at regular intervals throughout their lifespans, the researchers identified hundreds of genes that were expressed differently in microglia at each age. They also found that microglia from female mice displayed gradual changes during the aging process, while microglia from male mice showed a sudden transition from a young phenotype to an aged phenotype after 12 months.

To understand the aging process of microglial cells more precisely, the researchers mapped the epigenetic alterations of age-dependent microglia (ADEM) genes. They found that aged microglia were less responsive to immune-triggering substances compared to young microglia, indicating a decline in functionality.

To further investigate the contribution of aged-like microglia to cognitive decline and myelin impairment, the team used the 3xDR method to selectively deplete and repopulate microglial cells in the brain. They found that aged-like microglia per se were responsible for cognitive decline and myelin impairment.

While the study was conducted in mice, the researchers believe that their findings may have implications for understanding the aging process and disease mechanisms in humans. The data from the study is available publicly at MicrogliAtlas and could provide valuable insights into microglial aging and how these cells maintain brain function.

In conclusion, this research highlights the importance of understanding the aging process of microglial cells and its impact on brain health. By unraveling the mechanisms underlying microglial cell aging, researchers may be able to develop targeted interventions to prevent or treat brain dysfunction and cognitive decline in the future.


– Fudan University: Bo Peng
– Study: “Transcriptional and epigenetic decoding of the microglial aging process” published in Nature Aging.

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