論文 - 詳細
| RRC ID | 19656 |
|---|---|
| 著者 | Iwasa H, Yu S, Xue J, Driscoll M. |
| タイトル | Novel EGF pathway regulators modulate C. elegans healthspan and lifespan via EGF receptor, PLC-gamma, and IP3R activation. |
| ジャーナル | Aging Cell |
| Abstract |
Improving health of the rapidly growing aging population is a critical medical, social, and economic goal. Identification of genes that modulate healthspan, the period of mid-life vigor that precedes significant functional decline, will be an essential part of the effort to design anti-aging therapies. Because locomotory decline in humans is a major contributor to frailty and loss of independence and because slowing of movement is a conserved feature of aging across phyla, we screened for genetic interventions that extend locomotory healthspan of Caenorhabditis elegans. From a group of 54 genes previously noted to encode secreted proteins similar in sequence to extracellular domains of insulin receptor, we identified two genes for which RNAi knockdown delayed age-associated locomotory decline, conferring a high performance in advanced age phenotype (Hpa). Unexpectedly, we found that hpa-1 and hpa-2 act through the EGF pathway, rather than the insulin signaling pathway, to control systemic healthspan benefits without detectable developmental consequences. Further analysis revealed a potent role of EGF signaling, acting via downstream phospholipase C-gammaplc-3 and inositol-3-phosphate receptor itr-1, to promote healthy aging associated with low lipofuscin levels, enhanced physical performance, and extended lifespan. This study identifies HPA-1 and HPA-2 as novel negative regulators of EGF signaling and constitutes the first report of EGF signaling as a major pathway for healthy aging. Our data raise the possibility that EGF family members should be investigated for similar activities in higher organisms. |
| 巻・号 | 9(4) |
| ページ | 490-505 |
| 公開日 | 2010-8-1 |
| DOI | 10.1111/j.1474-9726.2010.00575.x |
| PII | ACE575 |
| PMID | 20497132 |
| PMC | PMC5859306 |
| MeSH | Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / metabolism* Caloric Restriction Diet Enzyme Activation Epidermal Growth Factor / metabolism* ErbB Receptors / metabolism* Genes, Helminth / genetics Health Inositol 1,4,5-Trisphosphate Receptors / metabolism* Insulin / metabolism Locomotion / physiology Longevity / physiology* Models, Biological Phospholipase C gamma / metabolism* RNA Interference Signal Transduction |
| IF | 7.238 |
| 引用数 | 52 |
| WOS 分野 | GERIATRICS & GERONTOLOGY CELL BIOLOGY |
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オルトメトリクス指標項目
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| 最多言及媒体 | Blogs |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm3256 tm3827 |