衰老药理学:果蝇作为验证健康寿命药物靶点的工具。

Eliano Dos Santos, Helena M Cochemé
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摘要

寻找有效的疗法来控制与年龄有关的疾病是一项新出现的公共卫生挑战。尽管针对疾病的治疗非常重要,但以衰老为重点的预防方法可能更有效。针对衰老相关过程的药物治疗可以延长动物模型的寿命并改善其健康状况。然而,药物开发和转化在老年科学中尤其具有挑战性。临床前研究将存活作为药物筛选的主要终点,这需要在哺乳动物模型中进行多年的研究。可以利用寿命较短的无脊椎动物来加速这一过程。尤其是果蝇,它可以利用精确的遗传工具验证新的药物靶点,并对影响保守衰老过程的药物进行概念验证实验。筛选作用于衰老相关靶点的临床批准药物可进一步加快转化速度,并为衰老研究创造新的工具。迄今为止,已有 31 种用于临床实践的药物被证明可以延长苍蝇的寿命。在这里,我们将介绍衰老药理学的最新进展,重点介绍果蝇作为一种工具来重新利用这些药物和研究与衰老相关的过程。
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Pharmacology of Aging: Drosophila as a Tool to Validate Drug Targets for Healthy Lifespan.

Finding effective therapies to manage age-related conditions is an emerging public health challenge. Although disease-targeted treatments are important, a preventive approach focused on aging can be more efficient. Pharmacological targeting of aging-related processes can extend lifespan and improve health in animal models. However, drug development and translation are particularly challenging in geroscience. Preclinical studies have survival as a major endpoint for drug screening, which requires years of research in mammalian models. Shorter-lived invertebrates can be exploited to accelerate this process. In particular, the fruit fly Drosophila melanogaster allows the validation of new drug targets using precise genetic tools and proof-of-concept experiments on drugs impacting conserved aging processes. Screening for clinically approved drugs that act on aging-related targets may further accelerate translation and create new tools for aging research. To date, 31 drugs used in clinical practice have been shown to extend the lifespan of flies. Here, we describe recent advances in the pharmacology of aging, focusing on Drosophila as a tool to repurpose these drugs and study age-related processes.

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