Preclinical models have been the backbone of translational research for more than a century. Rats and mice are critical models in the preliminary stages of drug testing, both for determining efficacy and ruling out potential human-relevant toxicities. Historically, most preclinical pharmacological studies have used young, relatively healthy, inbred male models in highly controlled environments. In the field of geriatric pharmacology, there is a growing focus on the importance of using more appropriate preclinical models both in the testing of therapeutics commonly used in older populations, and in the evaluation of potential geroprotective drug candidates. Here we provide a commentary on optimizing preclinical models of ageing for translation to clinical trials. We will discuss approaches to modelling clinically relevant contexts such as age, sex, genetic diversity, exposures and environment, as well as measures of clinically relevant outcomes such as frailty and healthspan. We will identify the strengths and limitations of these approaches and areas for improvement. We will also briefly cover new preclinical models that move beyond rodents. We hope this commentary will be a springboard for larger discussions on optimizing preclinical ageing models for testing therapeutics.
Longevity Relevance Analysis
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The paper discusses optimizing preclinical models of aging, which is pertinent to the field of longevity research as it aims to improve the translation of findings from animal models to human clinical trials. However, it primarily serves as a commentary rather than presenting original research or significant new findings. While it addresses important considerations in geriatric pharmacology, the impact is limited as it does not propose novel solutions or breakthroughs in understanding the root causes of aging or lifespan extension.