New Trends in Aging Drug Discovery

Abstract

Aging is considered the main risk factor for many chronic diseases that frequently appear at advanced ages. However, the inevitability of this process is being questioned by recent research that suggests that senescent cells have specific features that differentiate them from younger cells and that removal of these cells ameliorates senescent phenotype and associated diseases. This opens the door to the design of tailored therapeutic interventions aimed at reducing and delaying the impact of senescence in life, that is, extending healthspan and treating aging as another chronic disease. Although these ideas are still far from reaching the bedside, it is conceivable that they will revolutionize the way we understand aging in the next decades. In this review, we analyze the main and well-validated cellular pathways and targets related to senescence as well as their implication in aging-associated diseases. In addition, the most relevant small molecules with senotherapeutic potential, with a special emphasis on their mechanism of action, ongoing clinical trials, and potential limitations, are discussed. Finally, a brief overview of alternative strategies that go beyond the small molecule field, together with our perspectives for the future of the field, is provided.

Sex-Specific Protection of Endothelial Function after Vascular Ischemia/Reperfusion Injury by the Senomorphic Agent Ruxolitinib

“…In old age, severe cardiovascular events, even when treated adequately, may trigger frailty that many patients often cannot overcome. It was shown by other groups that the continuous treatment of old mice with ruxolitinib decreased frailty in old age [36]. This finding highlights that in old patients who have experienced a severe cardiovascular event, which is commonly associated with severe I/R injury, treatment with ruxolitinib from the onset of reperfusion and continuing long-term might be promising.…”

Senescence in Aging, Within the Brain and Other Diseases: Mechanisms and Interventions

“…228 On the other hand, senescent lung fibroblasts (IMR90) that had undergone ionizing radiation-induced senescence were reported to be specifically killed by RG-7112. 229 The natural substance ouabain, a member of the GC family of cardiac glycosides, was once thought to be a particular inhibitor of Na+ K+-ATPase, but later found to be a general senolytic drug. 230 Interestingly, lysosomal β-galactosidase (SA-β-gal) is often elevated, and this is mostly seen in SnCs.…”