Receptor Unit, Laboratory of Cardiovascular Sciences, National Institute on Aging, NIH, Baltimore, Maryland, USA.
Receptor Unit, Laboratory of Cardiovascular Sciences, National Institute on Aging, NIH, Baltimore, Maryland, USA,
Front Biosci (Landmark Ed). 2019 Jan 1;24(3):555-563. doi: 10.2741/4735.
The receptor for advanced glycation end products (RAGE) interacts with multiple ligands and transmits inflammatory signals from damage- and pathogen-associated molecular patterns (DAMPs and PAMPs) to cellular programs. RAGE shares ligands with another group of PRRs, Toll-like receptors. Such ligand-receptor promiscuity generates coordinated and complex signaling patterns that provide a basis for the development of multiple inflammaging diseases. Soluble RAGE (sRAGE) functions as a RAGE decoy that scavenges DAMP/PAMP ligands and dampens inflammatory signals. Epidemiological studies have shown that a lower level of circulating sRAGE is associated with metabolic syndromes including obesity, diabetes, hypertension, and subclinical brain disease. We hypothesize that an elevated level of circulating sRAGE serves to modulate systemic and low-grade chronical inflammation that often occurs in old age, and therefore minimizes the risk of inflammaing diseases. Consequently, a higher level of circulating sRAGE may improve the health-span of the organism. A newly generated transgenic mouse that has a higher level of circulating sRAGE and maintains normal expression levels of RAGE serves as a model to test this hypothesis.
晚期糖基化终产物受体（RAGE）与多种配体相互作用，并将损伤相关和病原体相关分子模式（DAMPs 和 PAMPs）的炎症信号传递给细胞程序。RAGE 与另一组 PRRs（Toll 样受体）共享配体。这种配体-受体的混杂性产生了协调和复杂的信号模式，为多种炎症老化疾病的发展提供了基础。可溶性 RAGE（sRAGE）作为 RAGE 诱饵，可清除 DAMPs/PAMPs 配体并抑制炎症信号。流行病学研究表明，循环中 sRAGE 水平较低与代谢综合征有关，包括肥胖、糖尿病、高血压和亚临床脑疾病。我们假设，循环中 sRAGE 水平升高可调节老年人常发生的全身性和低水平慢性炎症，从而最大限度地降低炎症性疾病的风险。因此，较高水平的循环 sRAGE 可能会改善机体的健康寿命。一种新生成的转基因小鼠具有较高水平的循环 sRAGE 并保持 RAGE 的正常表达水平，可作为测试该假设的模型。
