Banfield Kelley L, Gomez Tara A, Lee Wendy, Clarke Steven, Larsen Pamela L
Department of Cellular and Structural Biology, University of Texas Science Center at San Antonio, San Antonio, TX 78229, USA.
J Gerontol A Biol Sci Med Sci. 2008 Aug;63(8):798-808. doi: 10.1093/gerona/63.8.798.
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.
衰老过程中积累的蛋白质损伤可由一种修复甲基转移酶——L-异天冬氨酰-O-甲基转移酶减轻。在秀丽隐杆线虫中，pcm-1基因编码这种酶。我们发现，在信息素的作用下，由于甲基转移酶活性丧失，pcm-1突变体形成的滞育幼虫减少，存活率降低。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的滞育缺陷。此外，daf-2和daf-7突变体的滞育幼虫寿命明显长于野生型。虽然滞育幼虫对许多环境应激源具有抗性，但与20摄氏度相比，25摄氏度时滞育幼虫寿命的下降幅度相对更大，超过了成虫寿命的下降幅度。在25摄氏度时，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的过表达会延长成虫寿命。因此，决定滞育和成虫寿命的机制既有重叠又有不同。
