Aging-related Transcriptomic Changes with Spatial Resolution in the Human Prefrontal Cortex

bioRxiv (Cold Spring Harbor Laboratory) 2026 Preprint Open access

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Authors: Anupama Rai, Artemis Iatrou, Irais Valenzuela Arzeta, Alexandra Bartlett, Jane Banahan, Vedant Desai, Lorena Pantano, Isabel Castanho, Pourya Naderi Yeganeh, Athanasios Ploumakis, Shuoshuo Wang, Antonella Arruda de amaral
+12 more Nikolaos Kalavros, Sheethal Umesh Nagalakshmi, Peter Tsvetkov, Sabina Berretta, Isaac H. Solomon, Winston Hide, Ioannis S. Vlachos, Frank John Slack, Recep A Ozdemir, Shannan Ho Sui, Nikolaos Daskalakis, Maria Mavrikaki
DOI: 10.64898/2026.01.12.698703
Cited by: 1
References: 34

Abstract

Abstract The human prefrontal cortex (PFC), whose laminar organization is essential for cognitive function, is among the first regions to show age-related functional decline 1,2 . Single-cell sequencing studies revealed cell type–dependent aging effects but lacked spatial specificity 3–6 . Spatial transcriptomics (ST) advanced our molecular understanding of the human PFC 7 , 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.

Fields of Study & Subjects

Single-cell and spatial transcriptomics Memory and Neural Mechanisms Neuroinflammation and Neurodegeneration Mechanisms

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Publication date
12 January 2026
Language
EN
Document type
Preprint