Wang Ying-Zi, Guo Song-Yu, Kong Rui-Li, Sui Ao-Ran, Wang Zhen-Hua, Guan Rong-Xiao, Supratik Kundu, Zhao Jie, Li Shao
Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, China.
National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China.
Front Pharmacol. 2022 Jul 14;13:919269. doi: 10.3389/fphar.2022.919269. eCollection 2022.
Improving healthy life expectancy by targeting aging-related pathological changes has been the spotlight of geroscience. Scorpions have been used in traditional medicine in Asia and Africa for a long time. We have isolated heat-resistant peptides from scorpion venom of Buthusmartensii Karsch (SVHRP) and found that SVHRP can attenuate microglia activation and protect () against β-amyloid toxicity. Based on the amino acid sequence of these peptides, scorpion venom heat-resistant synthesized peptide (SVHRSP) was prepared using polypeptide synthesis technology. In the present study, we used as a model organism to assess the longevity-related effects and underlying molecular mechanisms of SVHRSP . The results showed that SVHRSP could prolong the lifespan of worms and significantly improve the age-related physiological functions of worms. SVHRSP increases the survival rate of larvae under oxidative and heat stress and decreases the level of reactive oxygen species and fat accumulation . Using gene-specific mutation of , we found that SVHRSP-mediated prolongation of life depends on Daf-2, Daf-16, Skn-1, and Hsf-1 genes. These results indicate that the antiaging mechanism of SVHRSP in nematodes might be mediated by the insulin/insulin-like growth factor-1 signaling pathway. Meanwhile, SVHRSP could also up-regulate the expression of stress-inducing genes Hsp-16.2, Sod-3, Gei-7, and Ctl-1 associated with aging. In general, our study may have important implications for SVHRSP to promote healthy aging and provide strategies for research and development of drugs to treat age-related diseases.
通过针对与衰老相关的病理变化来提高健康预期寿命一直是老年科学的研究热点。蝎子在亚洲和非洲的传统医学中已经被使用了很长时间。我们从东亚钳蝎的蝎毒中分离出耐热肽（SVHRP），并发现SVHRP可以减弱小胶质细胞的激活，并保护（此处原文缺失内容）免受β-淀粉样蛋白毒性的影响。基于这些肽的氨基酸序列，利用多肽合成技术制备了蝎毒耐热合成肽（SVHRSP）。在本研究中，我们以（此处原文缺失内容）作为模式生物来评估SVHRSP的长寿相关效应及其潜在的分子机制。结果表明，SVHRSP可以延长线虫的寿命，并显著改善线虫与年龄相关的生理功能。SVHRSP提高了幼虫在氧化应激和热应激下的存活率，并降低了活性氧水平和脂肪积累。通过对线虫进行基因特异性突变，我们发现SVHRSP介导的寿命延长依赖于Daf-2、Daf-16、Skn-1和Hsf-1基因。这些结果表明，SVHRSP在线虫中的抗衰老机制可能是由胰岛素/胰岛素样生长因子-1信号通路介导的。同时，SVHRSP还可以上调与衰老相关的应激诱导基因Hsp-16.2、Sod-3、Gei-7和Ctl-1的表达。总的来说，我们的研究可能对SVHRSP促进健康衰老具有重要意义，并为治疗与年龄相关疾病的药物研发提供策略。
