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测试证据表明,延长寿命的化合物干预措施在实验室动物模型物种中是保守的。

Testing the evidence that lifespan-extending compound interventions are conserved across laboratory animal model species.

机构信息

Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA.

Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, Texas, 78229, USA.

出版信息

Geroscience. 2023 Jun;45(3):1401-1409. doi: 10.1007/s11357-022-00722-0. Epub 2023 Jan 13.

Abstract

A growing number of pharmaceutical and small molecule interventions are reported to extend the lifespan of laboratory animals including Caenorhabditis, Drosophila, and mouse. However, the degree to which these pro-longevity interventions are conserved across species is unclear. Here, we took two approaches to ask the question: to what extent do longevity intervention studies in Caenorhabditis and Drosophila recapitulate effects on mouse lifespan? The first approach analyzes all published reports on longevity in the literature collated by the DrugAge database, and the second approach focused on results designed for reproducibility as reported from the NIA-supported Interventions Testing Program (ITP) and the Caenorhabditis Interventions Testing Program (CITP). Using published data sources, we identify only modest sensitivity and specificity of Drosophila interventional studies for identifying pro-longevity compounds in mouse lifespan studies. Surprisingly, reported studies in C. elegans show little predictive value for identifying drugs that extend lifespan in mice. The results therefore suggest caution should be used when making assumptions about the translatability of lifespan-extending compounds across species, including human intervention.

摘要

越来越多的药物和小分子干预措施被报道可以延长实验室动物的寿命,包括秀丽隐杆线虫、果蝇和小鼠。然而,这些延长寿命的干预措施在多大程度上在物种间得到保守尚不清楚。在这里,我们采用两种方法来提出这个问题:线虫和果蝇的长寿干预研究在多大程度上再现了对小鼠寿命的影响?第一种方法分析了由 DrugAge 数据库整理的文献中所有关于长寿的已发表报告,第二种方法则侧重于从 NIA 支持的干预测试计划 (ITP) 和秀丽隐杆线虫干预测试计划 (CITP) 中报告的旨在提高重现性的结果。使用已发表的数据来源,我们发现,在鉴定小鼠寿命研究中具有延长寿命作用的化合物方面,果蝇干预研究的敏感性和特异性仅适中。令人惊讶的是,报道的秀丽隐杆线虫研究表明,在鉴定能延长小鼠寿命的药物方面,其预测价值很小。因此,在做出关于跨物种(包括人类干预)延长寿命化合物的可转化性的假设时,应该谨慎。

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