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- W2977777874 abstract "Summary Immunosenescence is considered an inevitable decline in immune function during aging. Here we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically delays immunosenescence and rejuvenates immunity in C. elegans . We find that p38 mitogen-activated protein kinase 1 (PMK-1), a key determinant of immunosenescence, is dispensable for this rejuvenated immunity. Instead, we demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(-) animals. The upregulation of DAF-16/FOXO and HSF-1 decreases the expression of the zip - 10 /bZIP transcription factor, which in turn downregulates INS-7, an agonistic insulin-like peptide, resulting in further reduction of insulin/IGF-1 signaling (IIS). Thus, reduced IIS bypasses immunosenescence and rejuvenates immunity via the upregulation of anti-aging transcription factors that modulate an endocrine insulin-like peptide through a positive feedback mechanism. Because many functions of IIS are conserved across phyla, our study may lead to the development of strategies for human immune rejuvenation." @default.
- W2977777874 created "2019-10-10" @default.
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- W2977777874 date "2019-10-07" @default.
- W2977777874 modified "2023-10-17" @default.
- W2977777874 title "Reduction of insulin/IGF-1 receptor rejuvenates immunity via positive feedback circuit" @default.
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- W2977777874 doi "https://doi.org/10.1101/795781" @default.
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