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衰老药理学:作为验证健康寿命药物靶点的工具

Pharmacology of Aging: as a Tool to Validate Drug Targets for Healthy Lifespan.

作者信息

Dos Santos Eliano, Cochemé Helena M

机构信息

MRC Laboratory of Medical Sciences (LMS), London, UK.

Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, London, UK.

出版信息

Aging Biol. 2024 Sep 13;2(1):20240034. doi: 10.59368/agingbio.20240034.

Abstract

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 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 as a tool to repurpose these drugs and study age-related processes.

摘要

寻找有效的疗法来应对与年龄相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很重要,但专注于衰老的预防方法可能更有效。对与衰老相关过程进行药理学靶向可以延长动物模型的寿命并改善其健康状况。然而,在老年科学中,药物开发和转化尤其具有挑战性。临床前研究将生存作为药物筛选的主要终点,这需要在哺乳动物模型中进行数年的研究。寿命较短的无脊椎动物可用于加速这一过程。特别是,果蝇允许使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。筛选作用于与衰老相关靶点的临床批准药物可能会进一步加速转化,并为衰老研究创造新工具。迄今为止,已证明临床实践中使用的31种药物可延长果蝇的寿命。在此,我们描述了衰老药理学的最新进展,重点是将果蝇作为重新利用这些药物和研究与年龄相关过程的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa26/7616647/5e050dadb5b1/EMS198870-f004.jpg

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