@article{4076,
  keywords = {Animals, Caenorhabditis elegans, Signal Transduction, Down-Regulation, Aging, Transcriptional Activation, Caenorhabditis elegans Proteins, Forkhead Transcription Factors, Insulin, Longevity, Receptor, Insulin, Insulin-Like Growth Factor I, p38 Mitogen-Activated Protein Kinases, Up-Regulation, Basic-Leucine Zipper Transcription Factors},
  author = {Yujin Lee and Yoonji Jung and Dae-Eun Jeong and Wooseon Hwang and Seokjin Ham and Hae-Eun Park and Sujeong Kwon and Jasmine Ashraf and Coleen Murphy and Seung-Jae Lee},
  title = {Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop.},
  abstract = { <p>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.</p> },
  year = {2021},
  journal = {J Cell Biol},
  volume = {220},
  month = {2021 May 03},
  issn = {1540-8140},
  doi = {10.1083/jcb.202006174},
  language = {eng},
}