Microglial Replacement Reverses Age-Associated Epigenetic Modifications Despite Accelerating Epigenetic Age
Our brains contain specialized immune cells called microglia, which play a crucial role in maintaining brain health. As we age, these cells can accumulate changes that contribute to age-related brain disorders. Scientists have been exploring strategies to replace these older, less functional microglia with new ones, hoping to rejuvenate the brain. This recent research looked into how such a replacement strategy impacts the “epigenetic age” of these brain immune cells. Epigenetic age is like a biological clock that uses chemical tags on our DNA, called DNA methylation, to estimate an organism’s true biological age, which can be different from its chronological age. DNA methylation involves adding small chemical groups to DNA, which can influence gene activity without altering the genetic code itself. The study found that while replacing these old immune cells did cause an acceleration in one measure of epigenetic age, likely due to the rapid cell division needed for repopulation, it also remarkably reversed a large number of age-associated DNA methylation changes. These beneficial reversals were particularly observed in pathways linked to immune activation and inflammatory responses. This suggests that even if some biological age indicators seem to speed up, the overall effect of replacing these brain immune cells can lead to widespread reversal of aging-related molecular changes, which might explain the positive effects seen after such interventions.