Obstetrics and Gynecology, Hospital of Fudan University, Shanghai, 200011, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China.
Biogerontology. 2022 Aug;23(4):387-400. doi: 10.1007/s10522-022-09972-z. Epub 2022 Jun 21.
Cellular senescence, which is characterized by permanent proliferation arrest, has become an important target for the amelioration of various human diseases. The activity of senescent cells is mainly related to the senescence-associated secretory phenotype (SASP). The SASP can cause chronic inflammation in local tissues and organs through autocrine and paracrine mechanisms, and a series of factors secreted by senescent cells can deteriorate the cellular microenvironment, promoting tumor formation and exacerbating aging-related diseases. Therefore, avoiding the promotion of cancer is an urgent problem. In recent years, increased attention has been given to the mechanistic study of microRNAs in senescence. As important posttranscriptional regulators, microRNAs possess unique tissue-specific expression in senescence. MicroRNAs can regulate the SASP by regulating proteins in the senescence signaling pathway, the reverse transcriptase activity of telomerase, the generation of reactive oxygen species and oxidative damage to mitochondria. Numerous studies have confirmed that removing senescent cells does not cause significant side effects, which also opens the door to the development of treatment modalities against senescent cells. Herein, this review discusses the double-edged sword of cellular senescence in tumors and aging-related diseases and emphasizes the roles of microRNAs in regulating the SASP, especially the potential of microRNAs to be used as therapeutic targets to inhibit senescence, giving rise to novel therapeutic approaches for the treatment of aging-associated diseases.
细胞衰老的特征是永久性增殖停滞，已成为改善各种人类疾病的重要目标。衰老细胞的活性主要与衰老相关的分泌表型 (SASP) 有关。SASP 通过自分泌和旁分泌机制在局部组织和器官中引起慢性炎症，衰老细胞分泌的一系列因子可恶化细胞微环境，促进肿瘤形成并加剧与衰老相关的疾病。因此，避免促进癌症是一个紧迫的问题。近年来，人们越来越关注衰老过程中 microRNAs 的机制研究。作为重要的转录后调节因子，microRNAs 在衰老过程中具有独特的组织特异性表达。microRNAs 可以通过调节衰老信号通路中的蛋白质、端粒酶的逆转录酶活性、活性氧的产生以及线粒体氧化损伤来调节 SASP。大量研究证实，清除衰老细胞不会引起明显的副作用，这也为开发针对衰老细胞的治疗方法开辟了道路。本文讨论了细胞衰老在肿瘤和与衰老相关的疾病中的双刃剑作用，并强调了 microRNAs 在调节 SASP 中的作用，特别是 microRNAs 作为治疗靶点抑制衰老的潜力，为治疗与衰老相关的疾病提供了新的治疗方法。
