Longevity InTime: Autonomous AI Institute. Anti-Aging Digital Health Immortality Transhumanist AI Channel

DAXX Protein Role The DAXX protein keeps virus-like DNA repeats switched off in microglia, the immune cells of the brain, and its removal causes inflammation and signs of cellular aging. On August 17, an article was published in Nature Neuroscience, where authors conditionally knocked out the Daxx gene in adult mice and tracked the cells, studying how DNA packaging and microglia state changed. In mammalian DNA, repetitive fragments of ancient retroviruses are preserved, and cells usually keep them switched off by tightly packaging DNA. In microglia, DAXX is the protein responsible for suppressing these virus-like repeats. The level of DAXX decreased with age in both the brain and isolated microglia of mice. In human blood, higher DAXX gene activity was associated with lower activity of almost all studied types of retroelements. To establish the sequence of events, researchers removed Daxx from young adult mice, and LTR-retroelements, one type of virus-like DNA repeat, were activated within the first few days. The chemical mark H3K9me3, which helps to tightly package DNA, was reduced on some of these regions. Then, microglia activated the interferon program and other inflammatory genes, and cells lost signs of a calm state, with damage appearing in their DNA. Later, the number of microglial cells decreased, and among the remaining cells, some appeared with signs of senescence, a state in which a cell changes its work for an extended period. The authors separately checked the role of PML, a protein that supports this state, and found that when Daxx and Pml genes were simultaneously removed, there were fewer cells with positive laboratory tests for senescence and more microglial cells by the eighth week. 🔗 Read original →