Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy
Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy
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DOI：
10.18632/aging.102951
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发表时间：
2020-03-31
期刊：
影响因子：
5.2
通讯作者：
Li, Jian
中科院分区：
文献类型：
--
作者：
Liu, Wenwen;Lin, Huiling;Li, Jian
先前的证据表明，细胞内钙水平的增加促进细胞衰老。然而，钙通道阻滞剂（CCBs）是否可以延缓衰老和延长寿命仍然是未知的。在这项研究中，我们发现维拉帕米，一种L-型钙通道阻滞剂，延长了秀丽隐杆线虫（C。elegans）寿命和人肺成纤维细胞的延迟衰老。维拉帕米治疗也改善了C.几个年龄相关的生理参数，包括运动，颠簸，年龄相关的外阴完整性，和渗透胁迫抗性反映了这一点。我们还发现维拉帕米作用于C.优雅此外，维拉帕米通过抑制钙调磷酸酶活性延长蠕虫寿命。此外，维拉帕米显着促进自噬的LGG-1/LC 3的表达水平和自噬相关基因的mRNA水平反映。此外，当钙调磷酸酶基因tax-6被敲低时，维拉帕米不能进一步诱导自噬，表明维拉帕米诱导的寿命延长是通过促进钙调磷酸酶下游的自噬过程介导的。总之，我们的研究为维拉帕米在C.优雅
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.