A new preclinical paradigm for testing anti-aging therapeutics

W Ladiges, JM Snyder, E Wilkinson… - … Series A: Biomedical …, 2017 - academic.oup.com
W Ladiges, JM Snyder, E Wilkinson, DM Imai, T Snider, X Ge, M Ciol, C Pettan-Brewer…
Journals of Gerontology Series A: Biomedical Sciences and Medical …, 2017academic.oup.com
Testing drugs for anti-aging effects has historically been conducted in mouse life-span
studies, but are costly and time consuming, and more importantly, difficult to recapitulate in
humans. In addition, life-span studies in mice are not well suited to testing drug
combinations that target multiple factors involved in aging. Additional paradigms for testing
therapeutics aimed at slowing aging are needed. A new paradigm, designated as the
Geropathology Grading Platform (GGP), is based on a standardized set of guidelines …
Abstract
Testing drugs for anti-aging effects has historically been conducted in mouse life-span studies, but are costly and time consuming, and more importantly, difficult to recapitulate in humans. In addition, life-span studies in mice are not well suited to testing drug combinations that target multiple factors involved in aging. Additional paradigms for testing therapeutics aimed at slowing aging are needed. A new paradigm, designated as the Geropathology Grading Platform (GGP), is based on a standardized set of guidelines developed to detect the presence or absence of low-impact histopathological lesions and to determine the level of severity of high-impact lesions in organs from aged mice. The GGP generates a numerical score for each age-related lesion in an organ, summed for total lesions, and averaged over multiple mice to obtain a composite lesion score (CLS). Preliminary studies show that the platform generates CLSs that increase with the age of mice in an organ-dependent manner. The CLSs are sensitive enough to detect changes elicited by interventions that extend mouse life span, and thus help validate the GGP as a novel tool to measure biological aging. While currently optimized for mice, the GGP could be adapted to any preclinical animal model.
Oxford University Press