Establishing the relationship between brain cellular senescence and brain structure.

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.