Single-cell transcriptomic and genomic changes in the aging human brain.

Area of Science:

• Neuroscience
• Genomics
• Cell Biology

Background:

• Aging leads to cellular damage and dysregulation across tissues.
• Understanding transcriptomic and genomic changes in the aging human brain is crucial.

Approach:

• Utilized single-nucleus RNA-sequencing and single-cell whole-genome sequencing.
• Analyzed the prefrontal cortex across the human lifespan, from infancy to centenarian.

Key Points:

• Identified infant-specific cell clusters with high neurodevelopmental gene expression.
• Observed a common downregulation of essential homeostatic genes (ribosomes, transport, metabolism) with age.
• Detected decreased DNA repair gene expression and increased somatic mutations in aging brains.
• Found gene-length-specific somatic mutation rates influencing the aged brain's transcriptomic landscape.

Conclusions:

• Elucidates critical aspects of human brain aging at the transcriptomic and genomic levels.
• Highlights the dynamic interplay between genetic and expression changes throughout life.