Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop.

TitleReduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop.
Publication TypeJournal Article
Year of Publication2021
AuthorsLee, Y, Jung, Y, Jeong, D-E, Hwang, W, Ham, S, Park, H-EH, Kwon, S, Ashraf, JM, Murphy, CT, Lee, S-JV
JournalJ Cell Biol
Volume220
Issue5
Date Published2021 May 03
ISSN1540-8140
Abstract

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.

DOI10.1083/jcb.202006174
Alternate JournalJ Cell Biol
PubMed ID33666644
PubMed Central IDPMC7941181