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

2025 · doi:10.1101/2025.03.15.643430
preprint OA: closed
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The study constructed a spatio-temporal mouse brain microRNA atlas covering 15 regions and seven ages, using 1009 samples and including two aging interventions, to map how miRNA expression changes across lifespan. After establishing sex- and region-specific patterns in young adults, the authors analyzed sex-dependent and sex-independent age-associated changes and identified three sex-independent aging miRNAs: miR-146a-5p, miR-155-5p, and miR-5100. They specifically found that age-related increases in miR-155-5p are driven by aging microglia and that miR-155-5p is predicted to target components of the mTOR signaling pathway and other cellular communication pathways, while the main limitation is that the work is based on expression atlas mapping and does not demonstrate functional therapeutic efficacy. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Summary An in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease aging as a key risk factor for cognitive decline. Herein, we present a spatio-temporal brain atlas (15 different regions) of microRNA (miRNA) expression across the mouse lifespan (7 time points) and two aging interventions composed of 1009 samples. MiRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and are known to mediate aging speed. We first established sex- and brain-region-specific miRNA expression patterns in young adult samples. Then we focused on sex-dependent and independent brain-region-specific miRNA expression changes during aging. The corpus callosum in males and the choroid plexus in females exhibited strong sex-specific age-related signatures. In this work, we identified three sex-independent brain aging miRNAs (miR-146a-5p, miR-155-5p and miR-5100). We showed for miR-155-5p that these expression changes are driven by aging microglia. MiR-155-5p targets mTOR signaling pathway components and other cellular communication pathways and is hence a promising therapeutic target. Competing Interest Statement The authors have declared no competing interest.

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last seen: 2026-05-20T01:45:00.602351+00:00