A New Preclinical Paradigm for Testing Anti-Aging Therapeutics

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...

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Bibliographic Details
Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2017-06, Vol.72 (6), p.760-762
Main Authors: Ladiges, Warren, Snyder, Jessica M, Wilkinson, Erby, Imai, Denise M, Snider, Tim, Ge, Xuan, Ciol, Marcia, Pettan-Brewer, Christina, Pillai, Smitha P S, Morton, John, Quarles, Ellen, Rabinovitch, Peter, Niedernhofer, Laura, Liggitt, Denny
Format: Article
Language:English
Subjects:
Advisory Committees
Aged
Aging
Aging - drug effects
Aging - pathology
Animals
Biomedical Research
Clinical trials
Drug Evaluation, Preclinical - methods
Drugs
Histopathology
Humans
Life span
Pathology - methods
Research Practice
Rodents
Translational Medical Research
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Summary: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.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/glx019