Dasatinib and Quercetin, often referred to as a senolytic combination, are two distinct compounds studied for their synergistic effect in inducing apoptosis, or programmed cell death, specifically in senescent cells. Dasatinib is an FDA-approved tyrosine kinase inhibitor, while Quercetin is a naturally occurring flavonoid with potent antioxidant and anti-inflammatory properties. This pairing is clinically relevant in longevity research for its potential to clear detrimental senescent cells that accumulate with age and contribute to chronic disease.
Origin
Dasatinib is a synthesized pharmaceutical agent whose name reflects its chemical structure and therapeutic class as a kinase inhibitor. Quercetin is named after the oak species Quercus, from which it can be extracted, and its name reflects its chemical classification as a bioflavonoid. Their combined use as a senolytic therapy is a modern development, rooted in the biochemical understanding of cellular senescence and the search for compounds that can selectively eliminate these dysfunctional cells.
Mechanism
Senescent cells resist apoptosis and secrete a harmful mix of pro-inflammatory molecules known as the Senescence-Associated Secretory Phenotype (SASP). Dasatinib acts by inhibiting specific anti-apoptotic pathways, primarily in senescent fat cell precursors and endothelial cells, while Quercetin inhibits anti-apoptotic pathways in other cell types, such as senescent human umbilical vein endothelial cells. Administered together, this combination targets multiple pro-survival mechanisms within senescent cells, thereby forcing them into apoptosis and facilitating their clearance by the immune system, reducing systemic inflammation and potentially improving tissue function.
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