A hallmark of aging is immunosenescence, a decline in immune functions, which appeared to be inevitable in living organisms, including Caenorhabditis elegans. Here, we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically enhances immunocompetence in old age in C. elegans. We demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(-) animals. In contrast, p38 mitogen-activated protein kinase 1 (PMK-1), a key determinant of immunity, is only partially required for this rejuvenated immunity. The up-regulation of DAF-16/FOXO and HSF-1 decreases the expression of the zip-10/bZIP transcription factor, which in turn down-regulates INS-7, an agonistic insulin-like peptide, resulting in further reduction of insulin/IGF-1 signaling (IIS). Thus, reduced IIS prevents immune aging via the up-regulation of anti-aging transcription factors that modulate an endocrine insulin-like peptide through a feedforward mechanism. Because many functions of IIS are conserved across phyla, our study may lead to the development of strategies against immune aging in humans.

中文翻译：

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降低的胰岛素/ IGF1信号传导可通过ZIP-10 / bZIP介导的前馈环防止免疫衰老。

衰老的标志是免疫衰老，即免疫功能下降，这在包括秀丽隐杆线虫在内的生物中似乎是不可避免的。在这里，我们表明对DAF-2 /胰岛素/ IGF-1受体的遗传抑制作用可大大提高秀丽隐杆线虫的老年免疫能力。我们证明，长寿促进DAF-16 / FOXO和热休克转录因子1（HSF-1）增加老daf-2（-）动物的免疫能力。相比之下，p38促分裂原激活的蛋白激酶1（PMK-1），是免疫力的关键决定因素，对于这种恢复活力的免疫力仅部分需要。DAF-16 / FOXO和HSF-1的上调会降低zip-10 / bZIP转录因子的表达，进而下调INS-7（一种激动性的胰岛素样肽），导致胰岛素进一步减少/ IGF-1信令（IIS）。因此，降低的IIS通过上调抗衰老转录因子来防止免疫衰老，该因子通过前馈机制调节内分泌胰岛素样肽。由于IIS的许多功能在整个门系中都是保守的，因此我们的研究可能会导致开发针对人类免疫衰老的策略。