A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase
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.
Authors
- Oliver Hahn (ORCID: https://orcid.org/0000-0001-9440-1152)
- Nannan Lu (ORCID: https://orcid.org/0000-0003-0905-8199)
- Andreas Keller (ORCID: https://orcid.org/0000-0002-5361-0895)
- Tony Wyss‐Coray (ORCID: https://orcid.org/0000-0001-5893-0831)
- Nicole Ludwig (ORCID: https://orcid.org/0000-0003-4703-7567)
- Ulrike Fischer (ORCID: https://orcid.org/0000-0002-7808-9565)
- Aryaman Saksena (ORCID: https://orcid.org/0009-0002-1341-9428)
- Ian H. Guldner (ORCID: https://orcid.org/0000-0001-8715-136X)
- Eckart U. Meese (ORCID: https://orcid.org/0000-0001-7569-819X)
- Annika Engel (ORCID: https://orcid.org/0000-0001-5570-3115)
- Viktoria Wagner (ORCID: https://orcid.org/0000-0002-1957-0658)
- Aulden Foltz (ORCID: https://orcid.org/0000-0002-2983-2164)
- Micaiah Atkins (ORCID: https://orcid.org/0000-0003-0068-5217)
- Amila Beganovic
Institutions
- Neurosciences Institute (US)
- Enzo Life Sciences (United States) (US)
- Helmholtz Institute for Pharmaceutical Research Saarland (DE)
- Saarland University (DE)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-17
- DOI
- https://doi.org/10.1038/s41467-025-59860-6
- Citations
- 4
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- Michael J. Fox Foundation for Parkinson's Research
- American Heart Association
- Georgetown University
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Universität des Saarlandes
- National Institutes of Health
- Centro Nacional de Biotecnología