Research Paper|Volume 11, Issue 2|pp 771—782

The curcumin analog EF24 is a novel senolytic agent

Wen Li^1,^2,³, Yonghan He², Rongping Zhang¹, Guangrong Zheng⁴, Daohong Zhou²

¹School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan 650500, China
²Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
³Department of Endocrinology, The Third People’s Hospital of Yunnan Province, Kunming, Yunnan 650011, China
⁴Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA

Received: December 19, 2018Accepted: January 15, 2019Published: January 28, 2019

Copyright: © 2019 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.