Further Extension of Lifespan by Unc-43/CaMKII and Egl-8/PLCβ Mutations in Germline-Deficient Caenorhabditis elegans.

Further Extension of Lifespan by Unc-43/CaMKII and Egl-8/PLCβ Mutations in Germline-Deficient Caenorhabditis elegans.
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DOI:
10.3390/cells11223527
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发表时间:
2022-11-08
期刊:
影响因子:
6
通讯作者:
--
中科院分区:
生物学2区
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胰岛素/胰岛素样生长因子1(IGF 1)信号(IIS)的减少促进了跨物种的长寿。在线虫秀丽隐杆线虫中,生殖系干细胞(GSC)的消融和保守信号传导介质unc-43/CaMKII(钙/钙调蛋白依赖性激酶II型)和egl-8/PLCβ(磷脂酶Cβ)的活性变化也增加了寿命。与IIS一样,这些途径依赖于保守的转录因子daf-16/FOXO来延长寿命,但它们在功能上如何相互作用尚不清楚。在这里,我们表明,改变unc-43/egl-8活性进一步增加了长寿的GSC缺陷蠕虫的寿命,但不是由于胰岛素/IGF 1样受体daf-2的功能突变强烈减少而长寿的蠕虫。此外,我们提供了unc-43和egl-8在较小程度上调节某些胶原基因表达的证据,据报道,这些胶原基因与这些特定的daf-2突变体蠕虫的寿命有关,但与其他形式的寿命无关。总之,这些结果为CaMKII和PLCβ信号调节C的条件和潜在机制提供了新的见解。elegans寿命。
Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) promotes longevity across species. In the nematode Caenorhabditis elegans, ablation of germline stem cells (GSCs) and activity changes of the conserved signaling mediators unc-43/CaMKII (calcium/calmodulin-dependent kinase type II) and egl-8/PLCβ (phospholipase Cβ) also increase lifespan. Like IIS, these pathways depend on the conserved transcription factor daf-16/FOXO for lifespan extension, but how they functionally interact is unknown. Here, we show that altered unc-43/egl-8 activity further increases the lifespan of long-lived GSC-deficient worms, but not of worms that are long-lived due to a strong reduction-of-function mutation in the insulin/IGF1-like receptor daf-2. Additionally, we provide evidence for unc-43 and, to a lesser extent, egl-8 modulating the expression of certain collagen genes, which were reported to be dispensable for longevity of these particular daf-2 mutant worms, but not for other forms of longevity. Together, these results provide new insights into the conditions and potential mechanisms by which CaMKII- and PLCβ-signals modulate C. elegans lifespan.
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