目的：胰腺癌是一种高度恶性的肿瘤。尽管进行了广泛的研究，但与衰老相关的基因在PAAD的起始、微环境调节和进展中的确切作用仍不清楚。 方法：从国际癌症基因组联盟（ICGC）和癌症基因图谱（TCGA）队列中选择PAAD患者，细胞衰老相关基因从CellAge中获得。使用ConsensusClusterPlus进行群集识别。使用最小绝对收缩和选择算子（LASSO）Cox回归分析构建预后预测模型。 结果：我们基于与衰老相关的基因表达谱鉴定了三个群集（C1、C2和C3）。C1群集具有较短的总生存时间、较高的临床分级、较低的免疫ESTIMATE分数以及更严重的肿瘤免疫功能障碍和排斥（TIDE）分数。此外，C1群集中存在着细胞周期激活的信号通路富集。我们还鉴定了八个枢纽基因并构建了一个风险模型。细胞衰老相关特征（CSRS）得分高的亚型表现出较差的预后、更高的临床分级、M2巨噬细胞浸润、更高的免疫检查点基因表达以及更低的免疫治疗效益。 结论：我们的风险评分模型显示出在个体临床预后和免疫治疗前评估方面具有高的预测准确性和生存预测能力。

Objectives: Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor. Despite extensive research, the precise role of aging-related genes in the initiation, microenvironment regulation, and progression of PAAD remains unclear.Methods: Patients with PAAD were selected from the International Cancer Genome Consortium (ICGC), and The Cancer Genome Atlas (TCGA) cohorts and the cell senescence-associated genes were obtained from CellAge. ConsensusClusterPlus was utilized for cluster identification. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a prognosis prediction model.Results: We identified three clusters (C1, C2, and C3) based on aging-associated gene profiles. The C1 cluster had a shorter overall survival time, advanced clinical grades, lower immune ESTIMATE score, and tumor immune dysfunction and exclusion (TIDE) score than the C3 subgroup. Moreover, signaling pathways for cell cycle activation were enriched in the C1 cluster. We also identified eight hub genes and constructed a risk model. The high cellular senescence-related signature (CSRS) score subtype exhibited poor prognosis, advanced clinical grades, M2 macrophage infiltration, higher immune checkpoint gene expression, and lower immunotherapeutic benefits.Conclusion: Our risk score model shows high prediction accuracy and survival prediction ability in individual clinical prognosis and pre-immunotherapy evaluation.