Distinct cell-types in the prostate share an aging signature suggestive of metabolic reprogramming.
Distinct cell-types in the prostate share an aging signature suggestive of metabolic reprogramming.
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发表时间：
2020-08
影响因子：
1.2
通讯作者：
Preston D. Crowell;Jenna M. Giafaglione;T. Hashimoto;A. Goldstein
中科院分区：
文献类型：
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作者：
Preston D. Crowell;Jenna M. Giafaglione;T. Hashimoto;A. Goldstein
年龄是前列腺疾病的重要危险因素。然而，年龄增加疾病风险的机制尚未得到很好的描述。我们先前报道了小鼠前列腺的炎症和管腔内的年龄相关的变化。老年小鼠前列腺表现出Trop 2+管腔祖细胞群体的扩增以及Trop 2-管腔细胞的频率和功能能力的降低，表明不同的细胞类型对衰老具有不同的反应。前列腺中不同类型的细胞是否具有共同的衰老特征尚未确定。我们在年轻的成年小鼠和老年小鼠前列腺中转录分析了四种不同的细胞类型：基质细胞、基底细胞、Trop 2+管腔祖细胞和Trop 2-管腔细胞。在老年前列腺细胞类型中上调的基因的基序分析指出炎症和缺氧相关信号的转录调节因子。谷氨酸代谢和抗氧化反应是前列腺谱系衰老的共同标志。参与小鼠前列腺衰老的基因（包括抗氧化反应基因Hmox 1）的表达与TCGA队列中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共同特征，反映了与年龄相关的代谢重编程。
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 Hmox1, 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.