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

Author

Listed:
  • Annika Engel

    (Saarland University)

  • Viktoria Wagner

    (Saarland University
    Stanford University)

  • Oliver Hahn

    (Stanford University
    Calico Life Sciences LLC)

  • Aulden G. Foltz

    (Stanford University)

  • Micaiah Atkins

    (Stanford University)

  • Amila Beganovic

    (Saarland University)

  • Ian H. Guldner

    (Stanford University
    Stanford University School of Medicine)

  • Nannan Lu

    (Stanford University
    Stanford University School of Medicine)

  • Aryaman Saksena

    (Stanford University)

  • Ulrike Fischer

    (Saarland University)

  • Nicole Ludwig

    (Saarland University
    Saarland University)

  • Eckart Meese

    (Saarland University)

  • Tony Wyss-Coray

    (Stanford University
    Stanford University School of Medicine
    Stanford University)

  • Andreas Keller

    (Saarland University
    Helmholtz Center for Infection Research
    Saarland University)

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.

Suggested Citation

  • 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 , 2025. "A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59860-6
    DOI: 10.1038/s41467-025-59860-6
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    References listed on IDEAS

    as
    1. Raúl F. Pérez & Patricia Tezanos & Alfonso Peñarroya & Alejandro González-Ramón & Rocío G. Urdinguio & Javier Gancedo-Verdejo & Juan Ramón Tejedor & Pablo Santamarina-Ojeda & Juan José Alba-Linares & , 2024. "A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    2. Yalin Zhang & Min Soo Kim & Baosen Jia & Jingqi Yan & Juan Pablo Zuniga-Hertz & Cheng Han & Dongsheng Cai, 2017. "Hypothalamic stem cells control ageing speed partly through exosomal miRNAs," Nature, Nature, vol. 548(7665), pages 52-57, August.
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