1. A New Preclinical Paradigm for Testing Anti-Aging Therapeutics.
- Author
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Ladiges W, Snyder JM, Wilkinson E, Imai DM, Snider T, Ge X, Ciol M, Pettan-Brewer C, Pillai SPS, Morton J, Quarles E, Rabinovitch P, Niedernhofer L, and Liggitt D
- Subjects
- Advisory Committees, Aged, Aging pathology, Animals, Biomedical Research, Humans, Pathology methods, Translational Research, Biomedical, Aging drug effects, Drug Evaluation, Preclinical methods
- 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., (© The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
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