Science published an aging map of 40 human hippocampi: age-related changes affect microglia, astrocytes, and DNA folding
Science published an aging map of 40 human hippocampi: age-related changes affect microglia, astrocytes, and DNA folding
On July 23, Nathan Zemke’s team published a peer-reviewed paper in Science. The authors studied postmortem tissue from 40 people aged 20 to 100 and examined gene activity, chemical marks on DNA, and chromosome folding within the cell nucleus.
The hippocampus helps us remember events and navigate through space. Age-related changes in the brain are often discussed as a single overall measure, but the authors analyzed the tissue by cell type. They found that aging affects both the cellular composition of the hippocampus and how these cells regulate genes.
In samples from people aged 50–75, the proportion of microglia of embryonic origin was lower. Microglia are immune cells in the brain. They clear cellular debris, respond to damage, and help regulate neural connections. At the same time, cells with profiles resembling microglia derived from peripheral blood monocytes became more prominent. The proportion of astrocytes, which support signal transmission at synapses, was also lower.
This result is consistent with the SuperAgers map, which identified support programs in astrocytes and CA1 neurons in people over 80 who retained good memory. The new study examines the same cellular environment across the age range and documents a lower proportion of astrocytes in the hippocampus.
The most unusual finding concerns the three-dimensional organization of DNA. A chromosome is not stretched into a straight strand inside the nucleus. Distant regions of DNA can come into contact and jointly influence gene activity. In many cell types, this spatial organization became less distinct with age. The open-access author manuscript also describes a shift in microglia from a resting state to one primed for inflammation.
Within this single human cohort, the authors linked age-related changes in microglia and astrocytes to changes in gene regulation and DNA folding. The map presents hippocampal aging as a set of specific cellular changes rather than a single measure applied to the entire brain.