2024-09-03 マックス・プランク研究所
<関連情報>
- https://www.mpg.de/23417474/0903-pskl-ageing-brain-153150-x
- https://www.nature.com/articles/s41593-024-01742-z
ヒト眼窩前頭皮質の単一核トランスクリプトーム・プロファイリングにより、加齢と精神疾患の収束的影響が明らかになる Single-nucleus transcriptomic profiling of human orbitofrontal cortex reveals convergent effects of aging and psychiatric disease
Anna S. Fröhlich,Nathalie Gerstner,Miriam Gagliardi,Maik Ködel,Natan Yusupov,Natalie Matosin,Darina Czamara,Susann Sauer,Simone Roeh,Vanessa Murek,Chris Chatzinakos,Nikolaos P. Daskalakis,Janine Knauer-Arloth,Michael J. Ziller &Elisabeth B. Binder
Nature Neuroscience Published:03 September 2024
DOI:https://doi.org/10.1038/s41593-024-01742-z
Abstract
Aging 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.
