Senolysis is the selective pharmacological or immunological process of eliminating senescent cells (SnCs), which are aged, non-dividing cells that accumulate in tissues and secrete a detrimental pro-inflammatory mixture known as the Senescence-Associated Secretory Phenotype (SASP). This process is a key strategy in geroscience aimed at reducing the burden of SnCs to delay, prevent, or treat a wide array of age-related diseases and extend overall healthspan. Senolysis is achieved through the use of specific compounds collectively termed senolytics.
Origin
The term is a scientific neologism created from the Latin prefix ‘senex’, meaning old, and the Greek suffix ‘-lysis’, meaning to break down or destroy. It was coined by researchers in the longevity field to describe the targeted destruction of these non-functional cells. The concept gained significant traction following landmark studies demonstrating that the selective clearance of senescent cells from mice led to improvements in various markers of aging and disease.
Mechanism
Senolytics function by exploiting the unique pro-survival pathways that senescent cells activate to resist apoptosis, a phenomenon known as the Senescence Anti-Apoptotic Pathways (SAAPs). These pathways often involve the overexpression of anti-apoptotic proteins like the Bcl-2 family members. Senolytic drugs selectively inhibit these SAAPs, tipping the cell’s internal balance toward programmed cell death. This targeted inhibition causes the senescent cells to self-destruct while leaving surrounding healthy, non-senescent cells unharmed, thereby reducing the inflammatory burden of the SASP.
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