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A microRNA atlas of the human prefrontal cortex across the adult lifespan

Valenzuela-Arzeta, I. E.; Naderi Yeganeh, P.; Rai, A.; Banahan, J.; Iatrou, A.; Sejour, L.; Uyemura, M.; Solomon, I. H.; Daskalakis, N.; Vlachos, I.; Hide, W.; Slack, F. J.; Mavrikaki, M.

2026-05-28 neuroscience
10.64898/2026.05.27.728239 bioRxiv
Show abstract

Aging of the human brain is characterized by widespread changes in gene expression regulated in part by microRNAs (miRNAs). We present a lifespan miRNA atlas of the human dorsolateral prefrontal cortex generated from small RNA sequencing of 113 postmortem samples spanning 18 to 100 years of age. Differential expression analysis revealed progressive age-associated remodeling of miRNA expression, with the strongest differences observed between old and young individuals. Among the significantly altered miRNAs, miR-34a-5p emerged as one of the most robustly upregulated miRNAs in the aged cortex, alongside additional aging-associated miRNAs including miR-155-5p, miR-132-3p, miR-212-3p, miR-449a, and members of the miR-302 family. This atlas provides a resource for investigating miRNA dysregulation and small RNA regulatory networks during human cortical aging.

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