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

Annika Engel, Viktoria Wagner, Oliver Hahn, Aulden G. Foltz, Micaiah Atkins, Amila Beganovic, Ian H. Guldner, Nannan Lu, Aryaman Saksena, Ulrike Fischer, Nicole Ludwig, Eckart Meese, Tony Wyss-Coray and Andreas Keller ()
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Annika Engel: Saarland University
Viktoria Wagner: Saarland University
Oliver Hahn: Stanford University
Aulden G. Foltz: Stanford University
Micaiah Atkins: Stanford University
Amila Beganovic: Saarland University
Ian H. Guldner: Stanford University
Nannan Lu: Stanford University
Aryaman Saksena: Stanford University
Ulrike Fischer: Saarland University
Nicole Ludwig: Saarland University
Eckart Meese: Saarland University
Tony Wyss-Coray: Stanford University
Andreas Keller: Saarland University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract 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 expression across the mouse lifespan (7 time points) and two aging interventions. MicroRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and mediate aging speed. We first established sex- and brain-region-specific microRNA expression patterns in young adult samples. Then we focused on sex-dependent and independent brain-region-specific microRNA expression changes during aging. We identified three sex-independent brain aging microRNAs (miR-146a-5p, miR-155-5p, and miR-5100). For miR-155-5p, we showed that these expression changes are driven by aging microglia and target mTOR signaling pathway components and other cellular communication pathways. In this work, we identify strong sex-brain-region-specific aging microRNAs and microglial miR-155-5p as a promising therapeutic target.

Date: 2025
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DOI: 10.1038/s41467-025-59860-6

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