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. 中雷帕霉素摄入的基因型和性状特异性反应

Genotype and Trait Specific Responses to Rapamycin Intake in .

作者信息

Rohde Palle Duun, Bøcker Asbjørn, Jensen Caroline Amalie Bastholm, Bergstrøm Anne Louise, Madsen Morten Ib Juul, Christensen Sandra Læsø, Villadsen Steffan Balling, Kristensen Torsten Nygaard

机构信息

Department of Chemistry and Bioscience, Aalborg University, DK-9220 Aalborg, Denmark.

Department of Health Science and Technology, Aalborg University, DK-9220 Aalborg, Denmark.

出版信息

Insects. 2021 May 20;12(5):474. doi: 10.3390/insects12050474.

Abstract

Rapamycin is a powerful inhibitor of the TOR (Target of Rapamycin) pathway, which is an evolutionarily conserved protein kinase, that plays a central role in plants and animals. Rapamycin is used globally as an immunosuppressant and as an anti-aging medicine. Despite widespread use, treatment efficiency varies considerably across patients, and little is known about potential side effects. Here we seek to investigate the effects of rapamycin by using as model system. Six isogenic lines were assessed for their fecundity, male longevity and male heat stress tolerance with or without rapamycin treatment. The results showed increased longevity and heat stress tolerance for male flies treated with rapamycin. Conversely, the fecundity of rapamycin-exposed individuals was lower than for flies from the non-treated group, suggesting unwanted side effects of the drug in . We found strong evidence for genotype-by-treatment interactions suggesting that a 'one size fits all' approach when it comes to treatment with rapamycin is not recommendable. The beneficial responses to rapamycin exposure for stress tolerance and longevity are in agreement with previous findings, however, the unexpected effects on reproduction are worrying and need further investigation and question common believes that rapamycin constitutes a harmless drug.

摘要

雷帕霉素是雷帕霉素靶蛋白(TOR)通路的一种强效抑制剂,TOR是一种在植物和动物中起核心作用的进化保守蛋白激酶。雷帕霉素在全球范围内用作免疫抑制剂和抗衰老药物。尽管使用广泛,但不同患者的治疗效果差异很大,而且对其潜在副作用知之甚少。在此,我们试图通过使用[具体模型系统]来研究雷帕霉素的作用。对六个同基因品系在有或没有雷帕霉素处理的情况下,评估其繁殖力、雄性寿命和雄性热应激耐受性。结果显示,用雷帕霉素处理的雄蝇寿命延长且热应激耐受性增强。相反,接触雷帕霉素个体的繁殖力低于未处理组的果蝇,这表明该药物在[具体对象]中存在不良副作用。我们发现了基因型与处理之间相互作用的有力证据,这表明在雷帕霉素治疗方面采用“一刀切”的方法是不可取的。雷帕霉素对压力耐受性和寿命的有益反应与先前的研究结果一致,然而,对繁殖的意外影响令人担忧,需要进一步研究,并且质疑了雷帕霉素是一种无害药物的普遍观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0733/8161023/c12d464baf45/insects-12-00474-g001.jpg

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