The curcumin analog EF24 is a novel senolytic agent

Wen Li, Yonghan He, Rongping Zhang, Guangrong Zheng, Daohong Zhou

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Cellular senescence is a hallmark of aging because senescent cells (SCs) accumulate with aging and play a causative role in age-related diseases. Selectively eliminating SCs has been emerging as a new strategy for treating age-related diseases and extending healthspan. Curcumin and its analogs have some anti-aging activities. However, the mechanisms of their action have not been fully elucidated. In the present study, we investigated whether various curcumin analogs can function as a senolytic agent. The results from our studies show that among these curcumin analogs EF24 is the most potent and broad-spectrum senolytic agent. Mechanistically, EF24 selectively kills SCs by inducing SC apoptosis in a reactive oxygen species (ROS) production independent manner but associated with an increase in the proteasome degradation of the Bcl-2 anti-apoptotic protein family proteins known to play an important role in protecting SCs from apoptosis. In addition, EF24 can synergistically kill SCs with ABT-263, a Bcl-2 and Bcl-xl inhibitor and a known senolytic agent. These findings provide new insights into the mechanisms by which curcumin analogs function as an anti-aging agent and suggest that the curcumin analog EF24 has the potential to be used as a novel senolytic agent for the treatment of age-related diseases.

Original languageEnglish (US)
Pages (from-to)771-782
Number of pages12
JournalAging
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Keywords

  • Aging
  • Cellular senescence
  • Curcumin
  • EF24
  • Senolytic agent

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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