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Transcriptomics of cortical gray matter thickness decline during normal aging.

P Kochunov¹, J Charlesworth, A Winkler

¹Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA. pkochunov@mprc.umaryland.edu

|May 28, 2013

Summary

Gene expression activity influences brain structure changes during aging. Specific gene transcripts predict cortical gray matter thickness variability, suggesting aging involves reduced regeneration and increased neuroinflammation.

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Area of Science:

Neuroscience
Genetics
Aging Research

Background:

Cortical gray matter thickness (GMT) variability is a key indicator of brain aging.
Understanding the molecular underpinnings of GMT changes is crucial for aging research.

Purpose of the Study:

To investigate if transcriptional activity can predict cortical gray matter thickness (GMT) variability in normal cerebral aging.
To identify specific genes and pathways associated with GMT changes.

Main Methods:

Whole-transcriptome correlation analysis in 379 individuals of Mexican American descent.
Transcriptome data collected 17 years prior to neuroimaging (MRI) for GMT measurement.
Genome-wide gene transcriptome data (20,413 transcripts) and pathway enrichment analysis.

Main Results:

Eight genes (e.g., IGFBP3, LRRN3) passed transcriptome-wide significance for predicting GMT variability.
Four factors from these genes explained up to 35% of regional GMT variability.
Integrin signaling and three innate immune pathways were significantly associated with GMT.

Conclusions:

Gene expression related to cellular processes (proliferation, adhesion, differentiation) and inflammation predicts cortical GMT variability.
Normal brain aging may result from declining regenerative capacity and increased neuroinflammation.