Establishing the relationship between brain cellular senescence and brain structure.

Anina N Lund, Brian H Kopell, Negar Golestani, Eric Vornholt, Ryan C Thompson, Lora E Liharska, Yuyang Luo, Esther Cheng, You Jeong Park, Brian Fennessy, Lilian Wilkins, Deepak A Kaji, Hannah Silk, Kimia Ziafat, Alice Hashemi, Emily Moya, Claudia Feng, Lisa M Linares, Ariela Buxbaum Grice, Sabrina Xie, Marysia-Kolbe Rieder, Joseph Scarpa, Prashant Kota, Vanessa Cohen, Brendan Sullivan, Punit Shah, Weiping Ma, Jessica S Johnson, Gregory M Miller, Richard Searfoss, Nischal Mahaveer Chand, Pei Wang, Girish N Nadkarni, Niven R Narain, Eric J Nestler, Michael A Kiebish, Eric E Schadt, Alexander W Charney, Noam D Beckmann

Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Windreich Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. · pubmed

Paper

Abstract

Cellular senescence and brain atrophy are both associated with brain aging, suggesting these processes may share underlying biological mechanisms. This study investigated these mechanisms by integrating structural neuroimaging with gene and protein expression data from prefrontal cortex tissue collected from individuals who underwent neurosurgery. Cell-type-specific gene expression signatures associated with neuroimaging features and cellular senescence were identified and replicated in several independent datasets. Significant correlations between these signatures were observed in excitatory neurons and microglia, especially for volume-related features. These associations were also observed for excitatory neurons in an independent brain gene expression dataset from individuals below 5 years of age, implying a role for senescence during brain development. Together, this study provides a deep characterization of molecular signatures linking brain structure and cellular senescence across different life stages and suggests mechanisms supporting brain development may also contribute to volume reduction observed during aging.

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Research summary

The study identifies molecular signatures linking brain structure and cellular senescence across different life stages. This research is relevant as it explores the underlying biological mechanisms of cellular senescence in the brain, which may contribute to aging and age-related changes in brain structure.

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