Longevity & AgingHuman Brain Aging Mapped Cell by Cell from Infancy to Age 104
Researchers at UMass Chan Medical School performed single-nucleus RNA sequencing, single-cell whole-genome sequencing, and spatial transcriptomics on prefrontal cortex tissue from 19 donors aged 0.4 to 104 years. They found that aging universally suppresses housekeeping genes involved in ribosomes, transport, and metabolism across all brain cell types, while neuron-specific genes remain largely stable. Infant brains contain unique clusters of immature neurons and astrocytes expressing developmental genes. Two age-linked mutational signatures accumulate in neurons, preferentially affecting short, highly expressed genes—the very genes whose transcription declines most with age—suggesting a feedback loop between genomic damage and transcriptional decline.
