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
リソース情報
線虫 tm3256 tm3827