Senolytics

Senolytic drugs or senotherapeutic agents are the drugs that can selectively remove senescent cells (SC). SC resist apoptosis and up-regulate various anti-apoptotic pathways and generate pro-inflammatory senescence(definition)-associated secretory phenotypes (SASP), thus allowing them to survive. With aging, SC accumulate at the sites of multiple chronic disorders and lead to increased morbidity, mortality and health expenditures. Senolytics(definition) temporarily impair these senescent cell anti-apoptotic Pathways (SCAPs), causing cell death of those SC with SASP. Senolytics are considered as a ‘hit-and-run’ approach, as these agents can be administered intermittently as they take weeks to reaccumulate. The first generation senolytic agents such as dasatinib, quercetin, fisetin and navitoclax are identified using hypothesis or mechanism-based approach of drug discovery. So, senescent cell targeting can be a treatment option for aging-related disorders such as COPD. Recently, senolytic agents have recently drawn a lot of interest as a potential treatment for COPD. There is increasing evidence that COPD is an accelerated lung aging disease, which lead to aggregation of SC that have lost their ability to undergo repair and secretion of SASPs, which causes inflammation, aberrant repair, resulting in fibrosis, narrowing of airway, emphysema and respiratory failure in COPD. Senescent cells in COPD are responsible for causing oxidative stress, dysfunction in telomeres and damaging DNA. Various proposed senolytic drugs are known to activate various cell-signaling molecules promoting apoptosis and inhibit certain signaling molecules involved in promoting senescence and, thus, may play a role in improving COPD symptoms and reducing comorbidities. Targeting COPD with senolytic agents has shown beneficial effects during experimental research. Various treatment approaches targeting senescence are under development, however, clinical trials need to be conducted. Targeting the cellular senescence using the senolytic agents may be transformative to counteract COPD progression unless the clinical studies witness the effectiveness and low toxicity. This chapter focus on the role of senescence in COPD and various senolytic agents that may be used in management of COPD.