A Single-Cell Transcriptomic Profiling Unveils the Geroprotective Role of GRHL2 in Primate Prostate Aging
Release date:
2025-11-05
Description:
Prostate aging leads to benign prostatic hyperplasia or prostate cancer, whereas cellular and molecular mechanisms remain largely enigmatic, particularly in primates. We have delineated the aging-associated molecular signatures, highlighting increased cellular senescence, fibrosis, and inflammation. We identified the downregulation of GRHL2, a key transcription factor, as a critical initiator of senescence in prostate epithelial cells. This downregulation represses CDK19 transcription, subsequently releasing P53 from the CDK19-P53 complex sequestration and activating P21 transcription, which are essential steps in the cellular senescence pathway. Furthermore, GRHL2-based gene therapy delays prostate epithelial cell senescence and mitigates the aging phenotypes in prostate in vivo. Overall, our findings enhance the current understanding of prostate aging in primates and provide a foundation for developing targeted therapeutic strategies for human prostate aging and its associated disorders.
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Individuals & samples
Files
Submitter: Liu Guanghui / ghliu@ioz.ac.cn
Organization: Institute of Zoology, Chinese Academy of Sciences
Submission date: 2024-12-25
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HRA009832.xlsx