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

Rai, A., Iatrou, A., Valenzuela, I., Bartlett, A., Banahan, J., Desai, V., Pantano, L., Castanho, I., Naderi Yeganeh, P., Ploumakis, A., Wang, S., Arruda de Amaral, A., Kalavros, N., Umensh, S., Tsvetkov, P., Berretta, S., Solomon, I. H., Hide, W., Vlachos, I., Slack, F., Ozdemir, R. A., Ho Sui, S., Daskalakis, N., Mavrikaki, M.

Beth Israel Deaconess Medical Center, Harvard Medical School · biorxiv

Paper

Abstract

The human prefrontal cortex (PFC), whose laminar organization is essential for cognitive function, is among the first regions to show age-related functional decline1,2. Single-cell sequencing studies revealed cell type-dependent aging effects but lacked spatial specificity3-6. Spatial transcriptomics (ST) advanced our molecular understanding of the human PFC7, 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.

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Research summary

The paper claims to reveal aging mechanisms across cortical layers in the human prefrontal cortex. This research is relevant as it addresses the molecular changes associated with aging in a critical brain region, potentially identifying targets for interventions that could mitigate cognitive decline and extend healthspan.

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