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| Status |
Public on Feb 26, 2021 |
| Title |
FOXO and HSF1 rejuvenate immunity via positive feedback regulation of insulin/IGF-1 signaling |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
A hallmark of aging is immunosenescence, a decline in immune function that appeared to be inevitable. Surprisingly, here we show that genetic inhibition of DAF-2/insulin/IGF-1 receptor drastically delays immunosenescence and even rejuvenates immunity in C. elegans. We find that p38 mitogen activated protein kinase (PMK-1), a key determinant of immunosenescence in wild-type, 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 up-regulation of DAF-16/FOXO and HSF-1 decreases the expression of zip-10/bZip transcription factor, which in turn down-regulates ins-7, an agonistic insulin-like peptide, for further reduction in insulin/IGF-1 signaling (IIS). Thus, reduced IIS bypasses immunosenescence and rejuvenates immunity via up-regulating anti-aging transcription factors that regulate an endocrine insulin-like peptide through a positive feedback mechanism. Because many functions of IIS are conserved across phyla, our study may lead to developing strategies for immune rejuvenation in humans.
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| Overall design |
The investigation of the changes of gene expression in wild-type (WT) and daf-2(-) animals at day 1 (young) and day 9 (old) adulthood
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| Contributor(s) |
Lee Y, Jeong D, Hwang W, Ham S, Park HH, Kwon S, Jung Y, Lee SV |
| Citation(s) |
33666644 |
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| Submission date |
Sep 23, 2019 |
| Last update date |
May 28, 2021 |
| Contact name |
Seung-Jae V Lee |
| E-mail(s) |
seungjaevlee@kaist.ac.kr
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| Organization name |
KAIST
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| Department |
Biological Sciences
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| Lab |
Room 5216
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| Street address |
291 Daehak-ro
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| City |
Daejeon |
| ZIP/Postal code |
34141 |
| Country |
South Korea |
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| Platforms (1) |
| GPL18245 |
Illumina HiSeq 2500 (Caenorhabditis elegans) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA573686 |
| SRA |
SRP222977 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE137861_RAW.tar |
1.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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