Tackling cellular senescence by targeting miRNAs

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.