Title | Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Lee, Y, Jung, Y, Jeong, D-E, Hwang, W, Ham, S, Park, H-EH, Kwon, S, Ashraf, JM, Murphy, CT, Lee, S-JV |
Journal | J Cell Biol |
Volume | 220 |
Issue | 5 |
Date Published | 2021 05 03 |
ISSN | 1540-8140 |
Keywords | Aging, Animals, Basic-Leucine Zipper Transcription Factors, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Down-Regulation, Forkhead Transcription Factors, Insulin, Insulin-Like Growth Factor I, Longevity, p38 Mitogen-Activated Protein Kinases, Receptor, Insulin, Signal Transduction, Transcriptional Activation, Up-Regulation |
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> |
DOI | 10.1083/jcb.202006174 |
Alternate Journal | J Cell Biol |
PubMed ID | 33666644 |
PubMed Central ID | PMC7941181 |