Justice Jamie N, Cesari Matteo, Seals Douglas R, Shively Carol A, Carter Christy S
Department of Integrative Physiology, University of Colorado Boulder.
Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Toulouse, France. INSERM UMR1207, Université de Toulouse III Paul Sabatier, Toulouse, France.
J Gerontol A Biol Sci Med Sci. 2016 Oct;71(10):1243-53. doi: 10.1093/gerona/glv035. Epub 2015 Apr 23.
Despite dedicated efforts to identify interventions to delay aging, most promising interventions yielding dramatic life-span extension in animal models of aging are often ineffective when translated to clinical trials. This may be due to differences in primary outcomes between species and difficulties in determining the optimal clinical trial paradigms for translation. Measures of physical function, including brief standardized testing batteries, are currently being proposed as biomarkers of aging in humans, are predictive of adverse health events, disability, and mortality, and are commonly used as functional outcomes for clinical trials. Motor outcomes are now being incorporated into preclinical testing, a positive step toward enhancing our ability to translate aging interventions to clinical trials. To further these efforts, we begin a discussion of physical function and disability assessment across species, with special emphasis on mice, rats, monkeys, and man. By understanding how physical function is assessed in humans, we can tailor measurements in animals to better model those outcomes to establish effective, standardized translational functional assessments with aging.
尽管人们致力于寻找延缓衰老的干预措施,但在衰老动物模型中能显著延长寿命的最有前景的干预措施,在转化为临床试验时往往无效。这可能是由于物种之间主要结局的差异,以及确定转化的最佳临床试验范式存在困难。目前,包括简短标准化测试组在内的身体功能测量方法被提议作为人类衰老的生物标志物,可预测不良健康事件、残疾和死亡率,并且通常用作临床试验的功能结局。运动结局现在正被纳入临床前测试,这是朝着提高我们将衰老干预措施转化为临床试验的能力迈出的积极一步。为了进一步推动这些努力,我们开始讨论跨物种的身体功能和残疾评估,特别强调小鼠、大鼠、猴子和人类。通过了解人类如何评估身体功能,我们可以调整对动物的测量,以便更好地模拟这些结局,从而建立有效的、标准化的衰老转化功能评估。