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Aging

Discovery of piperlongumine as a potential novel lead for the development of senolytic agents.


PMID 27913811

Abstract

Accumulating evidence indicates that senescent cells play an important role in many age-associated diseases. The pharmacological depletion of senescent cells (SCs) with a "senolytic agent", a small molecule that selectively kills SCs, is a potential novel therapeutic approach for these diseases. Recently, we discovered ABT-263, a potent and highly selective senolytic agent, by screening a library of rationally-selected compounds. With this screening approach, we also identified a second senolytic agent called piperlongumine (PL). PL is a natural product that is reported to have many pharmacological effects, including anti-tumor activity. We show here that PL preferentially killed senescent human WI-38 fibroblasts when senescence was induced by ionizing radiation, replicative exhaustion, or ectopic expression of the oncogene

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