Park Jeong-Hwan, Lee Joo-Hyun, Park Jeong-Woo, Kim Dong-Yun, Hahm Jeong-Hoon, Nam Hong Gil, Bae Young-Seuk
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
Oncotarget. 2017 Jun 6;8(23):36950-36963. doi: 10.18632/oncotarget.16939.
Studies show that a decrease in protein kinase CK2 (CK2) activity is associated with cellular senescence. However, the role of CK2 in organism aging is still poorly understood. Here, we investigated whether protein kinase CK2 (CK2) modulated longevity in Caenorhabditis elegans. CK2 activity decreased with advancing age in the worms. Knockdown of kin-10 (the ortholog of CK2β) led to a short lifespan phenotype and induced age-related biomarkers, including retardation of locomotion, decreased pharyngeal pumping rate, increased lipofuscin accumulation, and reduced resistance to heat and oxidative stress. The long lifespan of age-1 and akt-1 mutants was significantly suppressed by kin-10 RNAi, suggesting that CK2 acts downstream of AGE-1 and AKT-1. Kin-10 knockdown did not further shorten the short lifespan of daf-16 mutant worms but either decreased or increased the transcriptional activity of DAF-16 depending on the promoters of the target genes, indicating that CK2 is an upstream regulator of DAF-16 in C. elegans. Kin-10 knockdown increased production of reactive oxygen species (ROS) in the worms. Finally, the ROS scavenger N-acetyl-L-cysteine significantly counteracts the lifespan shortening and lipofuscin accumulation induced by kin-10 knockdown. Therefore, the present results suggest that age-dependent CK2 downregulation reduces longevity by associating with both ROS generation and the AGE-1-AKT-1-DAF-16 pathway in C. elegans.
研究表明，蛋白激酶CK2（CK2）活性降低与细胞衰老相关。然而，CK2在生物体衰老中的作用仍知之甚少。在此，我们研究了蛋白激酶CK2（CK2）是否调控秀丽隐杆线虫的寿命。在这些线虫中，CK2活性随年龄增长而降低。敲低kin-10（CK2β的直系同源物）导致寿命缩短表型，并诱导与年龄相关的生物标志物，包括运动迟缓、咽泵血率降低、脂褐素积累增加以及对热和氧化应激的抗性降低。age-1和akt-1突变体的长寿命被kin-10 RNAi显著抑制，表明CK2在AGE-1和AKT-1下游起作用。敲低Kin-10并没有进一步缩短daf-16突变体线虫的短寿命，但根据靶基因的启动子，要么降低要么增加DAF-16的转录活性，表明CK2是秀丽隐杆线虫中DAF-16的上游调节因子。敲低Kin-10增加了线虫中活性氧（ROS）的产生。最后，ROS清除剂N-乙酰-L-半胱氨酸显著抵消了敲低kin-10所诱导的寿命缩短和脂褐素积累。因此，目前的结果表明，年龄依赖性的CK2下调通过与秀丽隐杆线虫中的ROS生成以及AGE-1-AKT-1-DAF-16途径相关联而降低寿命。
