Pathology assessment is necessary to validate translational endpoints in preclinical aging studies

Abstract

The Geropathology Research Network has established a plan to identify and use pathology-based surrogate endpoints for aging intervention in preclinical drug studies to provide a predictable and short-term anti-aging drug response in line with clinical trials. The plan involves pathological assessment of tissues and organs from strains of old mice, by independent pathology groups in a concurrent manner in order to characterize the changes in lesion incidence and severity in response to anti-aging drugs at specific time points. This approach allows for connection with translational endpoints of aging, such as serum factors and physiological parameters, between mice and humans. Preclinical drug testing is a critical component of the plan, designed to shorten testing times from lengthy lifespan studies by comparing lesion grades and composite scores in treated and placebo cohorts at cross-sectional time points. In conclusion, a geropathology-based preclinical testing program is a step toward assuring maximum utilization of translational resources and increasing predictability of efficacy of new or repurposed drugs for clinical aging intervention studies.