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
Department of Comparative Medicine, University of Washington, Seattle.
Department of Pathology, University of Washington, Seattle.
J Gerontol A Biol Sci Med Sci. 2017 Jun 1;72(6):760-762. doi: 10.1093/gerona/glx019.
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.
从历史上看，测试药物的抗衰老效果是在小鼠寿命研究中进行的，但成本高昂且耗时，更重要的是，难以在人体中重现。此外，小鼠寿命研究不太适合测试针对衰老过程中多个因素的药物组合。因此，需要其他测试旨在延缓衰老的疗法的范例。一种新的范例，称为老年病理学分级平台（GGP），基于一套标准化指南开发，用于检测老年小鼠器官中低影响组织病理学病变的存在与否，并确定高影响病变的严重程度。GGP为器官中每个与年龄相关的病变生成一个数值分数，将所有病变分数相加，并在多只小鼠中求平均值，以获得综合病变评分（CLS）。初步研究表明，该平台生成的CLS会随着小鼠年龄的增长而以器官依赖的方式增加。CLS足够灵敏，能够检测出延长小鼠寿命的干预措施所引发的变化，从而有助于验证GGP作为一种测量生物衰老的新工具。虽然目前GGP是针对小鼠进行优化的，但它可以适用于任何临床前动物模型。
