State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, China.
Institute of Materia Medica, Dali University, Dali, China.
Aging (Albany NY). 2020 Mar 24;12(6):5300-5317. doi: 10.18632/aging.102951.
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 () lifespan and delayed senescence in human lung fibroblasts. Verapamil treatment also improved healthspan in 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 α1 subunit of an L-type calcium channel in . 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 , 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 .
先前的证据表明，细胞内钙离子水平的增加会促进细胞衰老。然而，钙通道阻滞剂（CCBs）是否能延缓衰老并延长寿命尚不清楚。在这项研究中，我们表明，作为一种 L 型钙通道阻滞剂，维拉帕米可延长（秀丽隐杆线虫）寿命并延缓人肺成纤维细胞衰老。维拉帕米治疗还改善了健康寿命，表现在几个与年龄相关的生理参数上，包括运动、抽搐、与年龄相关的外阴完整性和耐渗透压能力。我们还发现维拉帕米作用于 L 型钙通道的 α1 亚基。此外，维拉帕米通过抑制钙调神经磷酸酶活性延长线虫寿命。此外，维拉帕米通过 LGG-1/LC3 的表达水平和自噬相关基因的 mRNA 水平显著促进自噬。此外，当敲低钙调神经磷酸酶基因时，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钙调神经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（秀丽隐杆线虫）中的抗衰老作用提供了机制见解。
