Robust differences in cortical cell type proportions across healthy human aging inferred through cross-dataset...

Area of Science:

• Neuroscience
• Genomics
• Aging Research

Background:

• Cognitive decline with age is linked to brain cell changes.
• Studying these cellular differences in healthy aging is difficult due to sample size limitations and cellular heterogeneity.
• Existing methods struggle to scale for comprehensive aging and cellular analyses.

Purpose of the Study:

• To investigate cell type-specific changes in the human frontal cortex during healthy aging.
• To quantify proportional shifts in various brain cell types across a wide age range.
• To establish a robust understanding of the cellular landscape of healthy brain aging.

Main Methods:

• Utilized cellular deconvolution techniques on bulk gene expression data from the frontal cortex.
• Analyzed a large dataset comprising 8 datasets, 6 cohorts, 1142 subjects, and 1429 samples (ages 15-90).
• Ensured robustness by comparing findings across bulk and single-nucleus datasets.

Main Results:

• Identified significant age-associated changes in relative cell type proportions.
• Observed a decrease in somatostatin- and vasoactive intestinal peptide-expressing interneurons.
• Detected an increase in astrocytes and other non-neuronal cells, with a U-shaped pattern for microglia.

Conclusions:

• Presents a comprehensive analysis of cortical cell type proportions in healthy aging.
• Demonstrates that aging profoundly impacts the cellular composition of the frontal cortex.
• Highlights the utility of cellular deconvolution for studying brain aging at scale.