文献类型：期刊文献

英文题名：Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy

作者：Liu, Wenwen[1];Lin, Huiling[1];Mao, Zhifan[1];Zhang, Lanxin[1];Bao, Keting[1];Jiang, Bei[2];Xia, Conglong[3];Li, Wenjun[4];Hu, Zelan[1];Li, Jian[1,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[2]Dali Univ, Inst Mat Med, Dali, Yunnan, Peoples R China;[3]Dali Univ, Coll Pharm & Chem, Dali, Yunnan, Peoples R China;[4]Natl Inst Biol Sci, Beijing, Peoples R China

年份：2020

卷号：12

期号：6

起止页码：5300

外文期刊名：AGING-US

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000522733300039)】；

基金：This study was supported by the Program for Professor of Special Appointment (Eastern Scholar TP2018025) at Shanghai Institutions of Higher Learning, the Innovative Research Team of High-level Local Universities in Shanghai, and the National Special Fund for the State Key Laboratory of Bioreactor Engineering (2060204).

语种：英文

外文关键词：verapamil; Caenorhabditis elegans; anti-aging; cell senescence; autophagy

摘要：Previous evidence has revealed that increase in intracellular levels of calcium promotes cellular senescence. However, whether calcium channel blockers (CCBs) can slow aging and extend lifespan is still unknown. In this study, we showed that verapamil, an L-type calcium channel blocker, extended the Caenorhabditis elegans (C. elegans) lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in C. elegans as reflected by several age-related physiological parameters, including locomotion, thrashing, age-associated vulval integrity, and osmotic stress resistance. We also found that verapamil acted on the alpha 1 subunit of an L-type calcium channel in C. elegans. Moreover, verapamil extended worm lifespan by inhibiting calcineurin activity. Furthermore, verapamil significantly promoted autophagy as reflected by the expression levels of LGG-1/LC3 and the mRNA levels of autophagy-related genes. In addition, verapamil could not further induce autophagy when tax-6, calcineurin gene, was knocked down, indicating that verapamil-induced lifespan extension is mediated via promoting autophagy processes downstream of calcineurin. In summary, our study provided mechanistic insights into the anti-aging effect of verapamil in C. elegans.