Crowell Preston D, Giafaglione Jenna M, Hashimoto Takao, Goldstein Andrew S
Molecular Biology Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA.
Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
Am J Clin Exp Urol. 2020 Aug 15;8(4):140-151. eCollection 2020.
Age is a significant risk factor for disease of the prostate. However, the mechanisms by which age increases disease risk have not been well described. We previously reported age-related changes within the inflammatory and luminal compartments of the mouse prostate. Old mouse prostates exhibit an expansion of the population of Trop2+ luminal progenitor cells and a reduction in the frequency and functional capacity of Trop2- luminal cells, indicating that different cell-types have distinct responses to aging. Whether distinct cell-types in the prostate share a common signature of aging has not been established. We transcriptionally profiled four distinct cell-types in young adult and old mouse prostates: stromal, basal, Trop2+ luminal progenitor and Trop2- luminal cells. Motif analysis of genes upregulated in old prostate cell-types pointed to transcriptional regulators of inflammatory and hypoxia-related signaling. Glutathione metabolism and the antioxidant response emerged as a common signature of aging across prostatic lineages. Expression of genes implicated in mouse prostate aging, including the antioxidant response gene , correlates with age of diagnosis in primary prostate tumors from the TCGA cohort. These findings reveal a common signature shared by distinct cell-types in the old prostate reflective of age-associated metabolic reprogramming.
年龄是前列腺疾病的一个重要风险因素。然而,年龄增加疾病风险的机制尚未得到充分描述。我们之前报道了小鼠前列腺炎症和管腔区室中的年龄相关变化。老年小鼠前列腺中Trop2+管腔祖细胞群体扩大,而Trop2-管腔细胞的频率和功能能力降低,这表明不同细胞类型对衰老有不同反应。前列腺中不同细胞类型是否共享共同的衰老特征尚未确定。我们对年轻成年和老年小鼠前列腺中的四种不同细胞类型进行了转录谱分析:基质细胞、基底细胞、Trop2+管腔祖细胞和Trop2-管腔细胞。对老年前列腺细胞类型中上调基因的基序分析指向炎症和缺氧相关信号的转录调节因子。谷胱甘肽代谢和抗氧化反应成为前列腺谱系衰老的共同特征。与小鼠前列腺衰老相关的基因表达,包括抗氧化反应基因,与来自TCGA队列的原发性前列腺肿瘤的诊断年龄相关。这些发现揭示了老年前列腺中不同细胞类型共享的一个共同特征,反映了与年龄相关的代谢重编程。