细胞衰老具有重要的生物学意义。细胞衰老以不可逆的细胞周期阻滞方式防止肿瘤的发生，是生物体内一种重要的抑癌机制。近年来研究发现细胞衰老与组织修复、胚胎发育、组织器官和个体衰老以及多种衰老相关疾病等病理生理过程都有密切关系。本课题的前期研究发现：一种对核苷酸类似物具有高度亲和力的细胞膜转运蛋白OCTN1在细胞衰老过程中表达显著上调，因此我们提出假设：OCTN1在衰老细胞中表达升高促进核苷酸类似物化疗药向细胞内的转运，加速其清除率，从而降低药物对肿瘤的毒性作用。我们选择临床上最常用的化疗药物吉西他滨作为研究对象，重点探讨：① 衰老细胞对吉西他滨清除是否具有促进作用；② 因为吉西他滨本身具有诱导正常细胞衰老的作用，所以我们观察长期使用该药物是否引起机体组织细胞衰老，从而升高其清除率，降低对胰腺癌的毒性作用。该研究不仅为老年人肿瘤化疗提供了新的治疗方案，而且为提高吉西他滨的治疗效果提供新的思路。

Cellular aging has important biological implications. Cellular senescence prevents tumorigenesis by irreversible cell cycle arrest and is an important tumor suppressor mechanism in vivo. In recent years, studies have found that cell senescence is closely related to pathological and physiological processes such as tissue repair, embryonic development, tissue and organ senescence, and various aging-related diseases. Preliminary studies have found that a cell membrane transporter OCTN1 with high affinity for nucleotide analogues is significantly up-regulated during cellular senescence, so we hypothesized that OCTN1 elevation in senescent cells promote the transport of the chemotherapeutic drug into the cell and accelerates the drug clearance, thereby reducing the toxic effect of the drug on the tumor. We selected gemcitabine, the most commonly used chemotherapy drug in clinical practice, and our researches focuses are as follows: (1) whether have senescent cells a promoting effect on gemcitabine clearance? (2) because gemcitabine itself has the effect of inducing normal cell senescence, we observe whether long-term use of the drug causes the body Tissue cell senescence, increases its clearance and reduces the toxic effects on pancreatic cancer. This study not only provides a new treatment plan for cancer chemotherapy in the elderly, but also provides new ideas for improving the therapeutic effect of gemcitabine.