A New Preclinical Paradigm for Testing Anti-Aging Therapeutics

Warren Ladiges, Jessica M. Snyder, Erby Wilkinson, Denise Imai, Tim Snider, Xuan Ge, Marcia Ciol, Christina Pettan-Brewer, Smitha P.S. Pillai, John Morton, Ellen Quarles, Peter Rabinovitch, Laura Niedernhofer, Denny Liggitt

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)760-762
Number of pages3
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume72
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

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Therapeutics
Drug Combinations
Animal Models
Guidelines
Pharmaceutical Preparations

Keywords

  • Aging
  • Aging lesions in mice
  • Anti-aging therapeutics
  • Geropathology Grading Platform
  • Preclinical drug testing

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

A New Preclinical Paradigm for Testing Anti-Aging Therapeutics. / Ladiges, Warren; Snyder, Jessica M.; Wilkinson, Erby; Imai, Denise; Snider, Tim; Ge, Xuan; Ciol, Marcia; Pettan-Brewer, Christina; Pillai, Smitha P.S.; Morton, John; Quarles, Ellen; Rabinovitch, Peter; Niedernhofer, Laura; Liggitt, Denny.

In: The journals of gerontology. Series A, Biological sciences and medical sciences, Vol. 72, No. 6, 01.06.2017, p. 760-762.

Research output: Contribution to journalArticle

Ladiges, W, Snyder, JM, Wilkinson, E, Imai, D, Snider, T, Ge, X, Ciol, M, Pettan-Brewer, C, Pillai, SPS, Morton, J, Quarles, E, Rabinovitch, P, Niedernhofer, L & Liggitt, D 2017, 'A New Preclinical Paradigm for Testing Anti-Aging Therapeutics', The journals of gerontology. Series A, Biological sciences and medical sciences, vol. 72, no. 6, pp. 760-762. https://doi.org/10.1093/gerona/glx019
Ladiges, Warren ; Snyder, Jessica M. ; Wilkinson, Erby ; Imai, Denise ; Snider, Tim ; Ge, Xuan ; Ciol, Marcia ; Pettan-Brewer, Christina ; Pillai, Smitha P.S. ; Morton, John ; Quarles, Ellen ; Rabinovitch, Peter ; Niedernhofer, Laura ; Liggitt, Denny. / A New Preclinical Paradigm for Testing Anti-Aging Therapeutics. In: The journals of gerontology. Series A, Biological sciences and medical sciences. 2017 ; Vol. 72, No. 6. pp. 760-762.
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