Single-nucleus transcriptomic profiling of human orbitofrontal cortex reveals convergent effects of aging and psychiatric disease

Author:

Fröhlich Anna S.ORCID,Gerstner NathalieORCID,Gagliardi Miriam,Ködel Maik,Yusupov Natan,Matosin Natalie,Czamara DarinaORCID,Sauer Susann,Roeh Simone,Murek VanessaORCID,Chatzinakos Chris,Daskalakis Nikolaos P.ORCID,Knauer-Arloth JanineORCID,Ziller Michael J.ORCID,Binder Elisabeth B.ORCID

Abstract

AbstractAging is a complex biological process and represents the largest risk factor for neurodegenerative disorders. The risk for neurodegenerative disorders is also increased in individuals with psychiatric disorders. Here, we characterized age-related transcriptomic changes in the brain by profiling ~800,000 nuclei from the orbitofrontal cortex from 87 individuals with and without psychiatric diagnoses and replicated findings in an independent cohort with 32 individuals. Aging affects all cell types, with LAMP5+LHX6+ interneurons, a cell-type abundant in primates, by far the most affected. Disrupted synaptic transmission emerged as a convergently affected pathway in aged tissue. Age-related transcriptomic changes overlapped with changes observed in Alzheimer’s disease across multiple cell types. We find evidence for accelerated transcriptomic aging in individuals with psychiatric disorders and demonstrate a converging signature of aging and psychopathology across multiple cell types. Our findings shed light on cell-type-specific effects and biological pathways underlying age-related changes and their convergence with effects driven by psychiatric diagnosis.

Publisher

Springer Science and Business Media LLC

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Aging and age-related disorders, cell by cell;Science Signaling;2024-09-10

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