Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex.

Nicholas X Sloan, Jason Mares, Aidan C Daly, Shaunice Grier, Imdadul Haq, Christopher A Jackson, Natalie Barretto, Obadele Casel, Kristy Kang, Shruti Khiste, Kennedy Harris, Jacqueline Eschbach, Benjamin T Fullerton, Courteney Mattison, Brhan Gebremedhin, Joana Petrescu, Lilian Coie, Maria Hauge Pedersen, Ke Zhang, Jian Shu, Andrew F Teich, Hasini Reddy, Colin P Smith, Yousin Suh, Vilas Menon, Hemali Phatnani

Department of Neurology, Columbia Irving Medical Center, New York, NY, USA; Motor Neuron Center, Columbia University, New York, NY, USA; Center for Genomics of Neurodegenerative Disease, New York Genome Center, New York, NY, USA. · pubmed

Paper

Abstract

We performed Visium spatial transcriptomics (ST) and single-nucleus RNA sequencing (snRNA-seq) on a cohort of nonpathological human tissues to uncover signatures of aging and senescence in the dorsolateral prefrontal cortex (dlPFC). In doing so, we identified gene expression changes characteristic of aged cortical layers. The cellular composition of the dlPFC also changed with age, with increased homeostatic astrocyte abundance and with decreased somatostatin (SST) inhibitory neurons. Nuclei from dlPFC cell types displayed a strong decline in oxidative phosphorylation- and cytoplasmic translation-related genes with age. Additionally, oligodendrocytes showed several hallmarks of senescence and a linear increase in CDKN2A expression with age. Combined analysis of ST and snRNA-seq datasets revealed astrocyte- and vascular cell-related gene expression programs in the white matter and layer 1 that were strongly enriched with age and for senescence-associated genes. These findings will help facilitate future studies exploring the role of senescent cell subpopulations in the aging brain.

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Research summary

The paper identifies gene expression changes and cellular composition alterations in the dorsolateral prefrontal cortex associated with aging. This research is relevant as it explores the biological signatures of aging and senescence, contributing to the understanding of the root causes of aging in the human brain.

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