A novel class of therapeutic interventions specifically designed to selectively induce apoptosis (programmed cell death) in senescent cells, often referred to as “zombie cells,” while carefully sparing healthy, functional cells. By clearing these dysfunctional cells, senolytic therapies aim to reduce the systemic burden of the Senescence-Associated Secretory Phenotype (SASP) and the chronic low-grade inflammation it causes. This is a leading, targeted strategy in the clinical pursuit of longevity and anti-aging.
Origin
The term combines the root seno- (old age) and -lytic (to destroy or break down), clearly describing the therapy’s function. The concept was first realized with the identification of small molecules that could target the anti-apoptotic pathways that senescent cells exploit to survive. This field represents a cutting-edge area of research in cellular aging and is rapidly transitioning into human clinical trials for age-related diseases.
Mechanism
Senescent cells upregulate specific anti-apoptotic pathways (e.g., BCL-2 family proteins) to resist death, which is a key vulnerability targeted by senolytic agents. These agents disrupt the protective mechanisms, causing the senescent cells to undergo apoptosis and die. The subsequent removal of these cells by the immune system reduces the systemic burden of pro-inflammatory cytokines and proteases, thereby rejuvenating the tissue microenvironment and improving organ function.
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