A Standardized Protocol for Mouse Longevity Studies in Preclinical Drug Development.

Although aging is increasingly recognized as a key factor in chronic disease management, preclinical drug development rarely incorporates direct assessments of lifespan. To date, no biotechnology company has conducted a full mouse lifespan study for a therapeutic agent prior to human clinical trials, despite widespread chronic use of many approved drugs. This oversight stems from a lack of standardized protocols for the incorporation of mouse lifespan studies, high costs, limited commercial incentives, and regulatory risks associated with long-term data. Here, we present a comprehensive and scalable protocol for conducting mouse longevity studies in the early stages of drug development. Being aware of monetary constraints in the drug discovery process, we propose a basic design for a longevity study on ~250 (176 males and 72 females) genetically heterogeneous mice (UM-HET3) per group, with survival curves as primary endpoint, and propose enhanced study design options only if budget allows. Our framework provides a standardized foundation for integrating longevity assessments into routine drug development, offering the potential to uncover long-term risks or benefits that traditional toxicology studies may overlook. Broad implementation of such protocols could support the development of safer and more effective therapeutics for chronic diseases, while opening new avenues for discovery of substances that could slow down the rate of aging, known as geroprotectors.