New research from the Lodato Lab maps changes in the aging human brain, cell by cell

A new study from the lab of Michael Lodato, PhD, published in Nature, sheds light on the molecular changes that occur in the human brain during the normal aging process at an extraordinary level of detail.

For the study, the Lodato lab obtained brain samples (specifically, prefrontal cortex) from 19 human donors, ranging in age from 0.4 to 104 years, from the National Institutes of Health NeuroBioBank repository. Using a trifecta of single-cell analysis technologies—single-nucleus RNA-sequencing, single-cell whole genome sequencing, and spatial transcriptomics—they generated a comprehensive catalog of age-related, cell-type specific changes in the transcriptomic and genomic landscape, creating an unprecedented map of the transformations that occur in the human brain across the lifespan.

The study identified cell clusters specifically in the infant brain that are enriched for the expression of neurodevelopmental genes, consistent with the idea that brain development continues after birth. They also found, unexpectedly, that expression of neuron-specific genes remains unchanged throughout life. However, they observed widespread downregulation of certain housekeeping genes during aging, with short, highly expressed housekeeping genes exhibiting high mutation rates, suggesting that a combination of gene length, gene function, and genome damage shapes the transcriptome of the aging brain.

Read the full article in Nature.