Aging-related Transcriptomic Changes with Spatial Resolution in the Human Prefrontal Cortex
The human prefrontal cortex (PFC), whose laminar organization is essential for cognitive function, is among the first regions to show age-related functional decline<sup>1,2</sup>. Single-cell sequencing studies revealed cell type-dependent aging effects but lacked spatial specificity<sup>3-6</sup>. Spatial transcriptomics (ST) advanced our molecular understanding of the human PFC<sup>7</sup>, yet whether aging-driven changes differ across PFC layers remains unclear. Here, we performed whole-transcriptome ST on postmortem PFC from 37 individuals across the adult lifespan. We mapped cortical layers and revealed aging mechanisms across layers. This represents one of the largest and most comprehensive lifespan ST analysis of the human PFC brain, offering crucial insight into how the brain ages and identifying potential molecular targets to mitigate cognitive aging and extend healthspan.
Authors
- Frank J. Slack (ORCID: https://orcid.org/0000-0001-8263-0409)
- Athanasios Ploumakis
- Isabel Castanho (ORCID: https://orcid.org/0000-0003-1413-626X)
- Ioannis S. Vlachos (ORCID: https://orcid.org/0000-0002-8849-808X)
- Maria Mavrikaki (ORCID: https://orcid.org/0000-0002-8646-5022)
- Lorena Pantano (ORCID: https://orcid.org/0000-0002-3859-3249)
- Sabina Berretta
- Anupama Rai (ORCID: https://orcid.org/0000-0002-2596-5154)
- Peter Tsvetkov (ORCID: https://orcid.org/0000-0002-7577-2342)
- Isaac H. Solomon (ORCID: https://orcid.org/0000-0003-3432-0902)
- Antonella Arruda de amaral (ORCID: https://orcid.org/0009-0000-7704-5352)
- Shannan Ho Sui
- Jane Banahan
- Pourya Naderi Yeganeh
- Sheethal Umensh
- Nikolaos Daskalakis
- Winston Hide
- Recep A Ozdemir
- Vedant Desai
- Nikolaos Kalavros
- Irais Valenzuela
- Alexandra Bartlett
- Shuoshuo Wang
Institutions
- Broad Institute (US)
- Boston University (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- McLean Hospital (US)
- Harvard Affiliated Emergency Medicine Residency (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-01-12
- DOI
- https://doi.org/10.64898/2026.01.12.698703
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00