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A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p

Annika Engel1, Viktoria Wagner1,2, Oliver Hahn2,3

  • 1Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.

Nature Communications
|May 17, 2025
PubMed

Insights

Scientists mapped microRNA (miRNA) expression in the aging mouse brain. They identified specific miRNAs, including microglial miR-155-5p, as potential therapeutic targets to combat age-related cognitive decline.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Aging Research

Background:

  • Aging is a significant risk factor for cognitive decline.
  • Understanding molecular aging processes is key to developing therapeutic interventions.
  • MicroRNAs (miRNAs) regulate gene expression and influence aging.

Purpose of the Study:

  • To create a spatio-temporal atlas of miRNA expression in the mouse brain across the lifespan.
  • To identify sex- and brain-region-specific miRNA changes during aging.
  • To explore potential therapeutic targets for age-related cognitive decline.

Main Methods:

  • Comprehensive analysis of miRNA expression across 15 brain regions and 7 time points in mice.
  • Investigation of miRNA expression patterns in young adults and during aging, considering sex differences.
  • Validation of specific miRNA roles, including miR-155-5p in microglia and its targeted pathways.

Main Results:

  • Established detailed sex- and brain-region-specific miRNA expression profiles.
  • Identified three key sex-independent brain aging miRNAs: miR-146a-5p, miR-155-5p, and miR-5100.
  • Demonstrated that aging microglia drive miR-155-5p expression changes, targeting mTOR signaling and cellular communication pathways.

Conclusions:

  • The study provides a valuable brain atlas of aging-related miRNA changes.
  • Microglial miR-155-5p is identified as a promising therapeutic target for mitigating age-related cognitive decline.
  • Understanding sex- and region-specific miRNA dynamics is crucial for targeted interventions.

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