Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
PLoS Genet. 2011 May;7(5):e1002082. doi: 10.1371/journal.pgen.1002082. Epub 2011 May 19.
The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans.
随着年龄的增长，免疫功能下降，即免疫衰老，这一现象在多种进化物种中都有体现，但其中的潜在分子机制尚不清楚。在秀丽隐杆线虫的衰老过程中，会观察到肠道组织恶化和细菌在肠道中的过度增殖，但秀丽隐杆线虫衰老过程中先天免疫如何变化尚不清楚。本文中，作者表明线虫随着年龄的增长，其对细菌感染的易感性增加，并证实衰老与保守的 PMK-1 p38 丝裂原活化蛋白激酶途径活性下降有关，该途径调节线虫的先天免疫。本文数据定义了秀丽隐杆线虫先天免疫衰老的现象，即 PMK-1 先天免疫信号通路随年龄的动态变化，并表明肠道组织衰老、免疫衰老和细菌增殖的循环导致衰老线虫的死亡。
