Reference - Detail
| RRC ID | 45946 |
|---|---|
| Author | Chen D, Li PW, Goldstein BA, Cai W, Thomas EL, Chen F, Hubbard AE, Melov S, Kapahi P. |
| Title | Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans. |
| Journal | Cell Rep |
| Abstract |
Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms. |
| Volume | 5(6) |
| Pages | 1600-10 |
| Published | 2013-12-26 |
| DOI | 10.1016/j.celrep.2013.11.018 |
| PII | S2211-1247(13)00685-2 |
| PMID | 24332851 |
| PMC | PMC3904953 |
| MeSH | AMP-Activated Protein Kinases / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Feedback, Physiological Forkhead Transcription Factors Germ Cells / metabolism* Germ-Line Mutation* Intestinal Mucosa / metabolism Longevity / genetics* Receptor, Insulin / genetics Receptor, Insulin / metabolism* Ribosomal Protein S6 Kinases, 70-kDa / genetics Ribosomal Protein S6 Kinases, 70-kDa / metabolism* Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 8.109 |
| Times Cited | 56 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 74 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1714 |