Protein-repair and hormone-signaling pathways specify dauer and adult longevity and dauer development in Caenorhabditis elegans
Protein-repair and hormone-signaling pathways specify dauer and adult longevity and dauer development in Caenorhabditis elegans
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DOI：
10.1093/gerona/63.8.798
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发表时间：
2008-08-01
影响因子：
5.1
通讯作者：
Larsen, Pamela L.
中科院分区：
文献类型：
--
作者：
Banfield, Kelley L.;Gomez, Tara A.;Larsen, Pamela L.
在衰老过程中积累的蛋白质损伤可以通过修复甲基转移酶（L-异戊酰-O-甲基转移酶）来减轻。在秀丽隐杆线虫中，pcm-1基因编码这种酶。在信息素的反应，我们表明，pcm-1突变体形成较少的dauer幼虫减少生存由于甲基转移酶活性的损失。胰岛素/胰岛素样生长因子1样受体daf-2和转化生长因子β样配体daf-7的突变可调节pcm-1 dauer缺陷。此外，daf-2和daf-7突变体dauer幼虫的寿命明显长于野生型。虽然幼虫对许多环境压力有抵抗力，但与20摄氏度相比，25摄氏度下幼虫寿命的下降幅度比成虫寿命大。在25 ℃时，daf-7或pcm-1基因的突变不会改变成虫寿命，而daf-2基因的突变和PCM-1的过表达会增加成虫寿命。因此，有重叠和不同的机制，指定dauer和成人寿命。
Protein damage that accumulates during aging can be mitigated by a repair methyltransferase, the L-isoaspartyl-O-methyltransferase. In Caenorhabditis elegans, the pcm-1 gene encodes this enzyme. In response to pheromone, we show that pcm-1 mutants form fewer dauer larvae with reduced survival due to loss of the methyltransferase activity. Mutations in daf-2, an insulin/insulin-like growth factor-1-like receptor, and daf-7, a transforming growth factor-beta-like ligand, modulate pcm-1 dauer defects. Additionally, daf-2 and daf-7 mutant dauer larvae live significantly longer than wild type. Although dauer larvae are resistant to many environmental stressors, a proportionately larger decrease in dauer larvae life spans occurred at 25 degrees C compared to 20 degrees C than in adult life span. At 25 degrees C, mutation of the daf-7 or pcm-1 genes does not change adult life span, whereas mutation of the daf-2 gene and overexpression of PCM-1 increases adult life span. Thus, there are both overlapping and distinct mechanisms that specify dauer and adult longevity.