Reduced insulin/igf1 signaling prevents immune aging via zip-10/bzip–mediated feedforward loop

Yujin Lee, Yoonji Jung, Dae Eun Jeong, Wooseon Hwang, Seokjin Ham, Hae Eun H. Park, Sujeong Kwon, Jasmine M. Ashraf, Coleen T. Murphy, Seung Jae V. Lee

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Article numbere202006174
JournalJournal of Cell Biology
Issue number5
StatePublished - May 3 2021

All Science Journal Classification (ASJC) codes

  • Cell Biology


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