Ladiges Warren
Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Aging Pathobiol Ther. 2024 Dec;6(4):152-153. doi: 10.31491/apt.2024.12.162. Epub 2024 Dec 28.
Efficient and reproducible preclinical models for testing drugs or drug combinations that target aging are vital to develop a pipeline that results in a predictable outcome for geroscience research and geriatric medicine. Lifespan as a readout test in laboratory mice has been successful in identifying several drugs that robustly enhance healthy aging, and has provided impactful information for moving to clinical studies. However, it is a costly and time consuming process (about three years), and poorly designed to test drug combinations. Therefore, a more efficient pipeline is needed that would provide an increased number of drugs or drug combinations with promising and predictable outcomes for first in human studies in a shorter time frame. This editorial discusses an alternate system involving prescreening in an invertebrate model (the domestic house cricket) followed by short term cross sectional testing in aging mice. The time frame is about six months, and the system is simple enough to allow testing of multiple drugs concurrently. The cricket to mouse pipeline provides a logical and preclinical translational approach to identify drugs that have the potential to enhance human health at later ages of life.
用于测试针对衰老的药物或药物组合的高效且可重复的临床前模型对于开发一条能为老年科学研究和老年医学带来可预测结果的产品线至关重要。在实验室小鼠中,将寿命作为一项读出测试已成功鉴定出几种能有力促进健康衰老的药物,并为推进到临床研究提供了有影响力的信息。然而,这是一个成本高昂且耗时的过程(约三年),而且在测试药物组合方面设计欠佳。因此,需要一个更高效的流程,该流程能在更短的时间内为首次人体研究提供更多具有有前景且可预测结果的药物或药物组合。这篇社论讨论了一种替代系统,该系统包括在无脊椎动物模型(家蟋蟀)中进行预筛选,然后在衰老小鼠中进行短期横断面测试。这个时间框架约为六个月,并且该系统足够简单,能够同时测试多种药物。从蟋蟀到家鼠的流程提供了一种合乎逻辑的临床前转化方法,以识别有可能在人类晚年增强健康的药物。