Reprogramming the GRHL2-CDK19 axis by gene therapy alleviates prostate aging.

Guoqiang Sun, Zan He, Dongliang Lv, Qiaoran Wang, Gang Xu, Feifei Liu, Peiyu Wang, Bilan Luo, Yandong Zheng, Jinghao Hu, Shuhui Sun, Shuai Ma, Concepcion Rodriguez Esteban, Jiayin Yang, Xiaobing Fu, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Jing Qu, Si Wang, Guang-Hui Liu

State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. · pubmed

Paper

Abstract

The prostate is a multifunctional organ of the male reproductive system whose aging process impairs sexual and urinary function and fertility and increases disease susceptibility, thereby compromising quality of life. However, the mechanisms underlying human prostate aging remain poorly understood. Here we integrated single-nucleus transcriptomics and histological analyses to elucidate the aging mechanisms of the primate prostate. We identified epithelial cell senescence, chronic inflammation and fibrosis as key hallmarks of prostate aging. In young epithelial cells, GRHL2 promotes CDK19 transcription, which sequesters p53, leading to the suppression of p21

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Research summary

The paper claims that reprogramming the GRHL2-CDK19 axis through gene therapy can alleviate prostate aging. This research addresses mechanisms underlying prostate aging, which is directly related to the biological processes of aging and potential interventions to mitigate age-related decline.

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