Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop
| العنوان: | Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop |
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| المؤلفون: | Yujin Lee, Yoonji Jung, Seokjin Ham, Hae-Eun H. Park, Sujeong Kwon, Wooseon Hwang, Seung-Jae Lee, Jasmine Ashraf, Coleen T. Murphy, Dae-Eun Jeong |
| المصدر: | The Journal of Cell Biology |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Transcriptional Activation, endocrine system, Aging, Physiology, medicine.medical_treatment, Longevity, Down-Regulation, p38 Mitogen-Activated Protein Kinases, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cell Signaling, RNA interference, Report, medicine, Animals, Insulin, Insulin-Like Growth Factor I, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Transcription factor, 030304 developmental biology, 0303 health sciences, biology, fungi, Forkhead Transcription Factors, Cell Biology, Immunosenescence, biology.organism_classification, Receptor, Insulin, Cell biology, Up-Regulation, Basic-Leucine Zipper Transcription Factors, Immunocompetence, Signal transduction, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | Immunosenescence, or immune aging, is a hallmark of aging. This study shows that inhibition of insulin/IGF-1 receptor reverses immunosenescence in the roundworm Caenorhabditis elegans through a feedback circuit comprising FOXO, HSF-1, and bZIP transcription factors and an insulin-like peptide, INS-7. 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. |
| تدمد: | 1540-8140 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ab260f8f6af91da59d4b0953f1b71a4 https://pubmed.ncbi.nlm.nih.gov/33666644 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6ab260f8f6af91da59d4b0953f1b71a4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 |
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