Cellular senescence is a complex and multistep biological process which cells can undergo in response to different stresses. Referring to a highly stable cell cycle arrest, cellular senescence can influence a multitude of biological processes—both physiologically and pathologically. While phenotypically diverse, characteristics of senescence include the expression of the senescence-associated secretory phenotype, cell cycle arrest factors, senescence-associated β-galactosidase, morphogenesis, and chromatin remodelling. Persistent senescence is associated with pathologies such as aging, while transient senescence is associated with beneficial programmes, such as limb patterning. With these implications, senescence-based translational studies, namely senotherapy and pro-senescence therapy, are well underway to find the cure to complicated diseases such as cancer and atherosclerosis. Being a subject of major interest only in the recent decades, much remains to be studied, such as regarding the identification of unique biomarkers of senescent cells. This review attempts to provide a comprehensive understanding.
Senotherapy is concerned with the development of therapeutic strategies to slowthe ageing process and alleviate its associated diseases by preventing, eliminating, or reversing senescence in cells . Although much of this study is still exploratory, and no drugs have been approved for clinical use, many different strategies have been identified.Central to all is the use of senolytics. Senolytic therapy is one of the more, if not the most, rapidly developing strategy for senotherapy. Senolytic agents are a class of small molecules that have been found to be able to selectively induce the apoptosis of senescent cells by interfering with the SCAPs. Most senolytic drugs that have been identified so far are repurposed anti-cancer drugs, such as the likes of dasatinib and quercetin (used in combination)—the first few senolytics to be discovered. The combination of these two drugs has been widely demonstrated to induce the apoptosis of senescent cells in cultured human tissues and in mouse models [146–148]. In one of the mouse models,the bi-weekly administration of dasatinib and quercetin on aged mice showed a 36% higher median lifespan, while the mortality hazard was reduced to 64.9% . This potential of the senolytic drugs has also been replicated in clinical trials—in the first-of-itskind Phase 1 clinical trial, the administration of dasatinib and quercetin on patients withidiopathic pulmonary fibrosis (IPF; a lung disease in which scarring of the lungs reduces their function) showed a significant improvement in physical functions (such as walking endurance) in the participants . The following subsections briefly discusses some potential senolytics and some recent findings. The information is summarised in Table.
关键词: senescence; cancer; aging; senotherapy 衰老；癌症；老化; 声疗