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  3. Aging-related Transcriptomic Changes With Spatial Resolution In The Human Prefrontal Cortex.
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  3. Aging-related Transcriptomic Changes With Spatial Resolution In The Human Prefrontal Cortex.

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Aging-related Transcriptomic Changes with Spatial Resolution in the Human Prefrontal Cortex.

Anupama Rai1, Artemis Iatrou1,2,3,4, Irais Valenzuela Arzeta1

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Biorxiv : the Preprint Server for Biology
|February 6, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

Aging affects the human prefrontal cortex (PFC) differently across its layers. This study used spatial transcriptomics to reveal layer-specific aging mechanisms in the PFC, identifying targets to improve cognitive aging and healthspan.

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Area of Science:

  • Neuroscience
  • Genomics
  • Aging Research

Background:

  • The human prefrontal cortex (PFC) is crucial for cognition but shows early age-related decline.
  • Previous studies lacked spatial resolution to understand layer-specific aging.
  • Spatial transcriptomics (ST) offers potential for layer-resolved analysis.

Purpose of the Study:

  • To investigate age-related molecular changes across different layers of the human PFC.
  • To identify layer-specific aging mechanisms within the PFC.
  • To discover molecular targets for mitigating cognitive aging.

Main Methods:

  • Whole-transcriptome spatial transcriptomics (ST) was performed on postmortem PFC samples.
  • Samples were obtained from 37 individuals spanning the adult lifespan.
  • Cortical layers were mapped to analyze aging patterns spatially.

    • Main Results:

    • Aging effects were found to differ significantly across the distinct layers of the PFC.
    • Specific molecular mechanisms driving aging were identified within each layer.
    • This study provides a comprehensive, layer-resolved map of PFC aging.

    Conclusions:

    • The human PFC exhibits layer-specific aging, impacting cognitive function.
    • Understanding these layer-specific changes is key to addressing cognitive decline.
    • Identified molecular targets may offer new strategies for enhancing brain healthspan.