Kane Alice E, Shin Sooyoun, Wong Aimee A, Fertan Emre, Faustova Natalia S, Howlett Susan E, Brown Richard E
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada.
Front Aging Neurosci. 2018 Jun 12;10:172. doi: 10.3389/fnagi.2018.00172. eCollection 2018.
Mouse models of Alzheimer's disease (AD) exhibit marked differences in life expectancy depending on their genotype and sex. The assessment of frailty could provide a measure of healthspan to facilitate comparisons between different AD models. We used a validated mouse frailty index (FI) assessment tool to explore genotype and sex differences in lifespan and healthspan of 3xTg-AD mice and their B6129F2 wild-type (WT) controls. This tool is based on an approach commonly used in people and quantifies frailty by counting the accumulation of age-related health deficits. The number of deficits in an individual divided by the total number measured yields an FI score theoretically between 0 and 1, with higher scores denoting more frailty. Male 3xTg-AD mice aged 300-600 days had higher FI scores (Mean FI = 0.21 ± 0.03) than either male WT (Mean FI = 0.15 ± 0.01) or female 3xTg-AD mice (Mean FI = 0.10 ± 0.01), and the elevated frailty scores were accompanied by parallel increases in mortality. Frailty increased exponentially with age, and higher rates of deficit accumulation elevated mortality risk in all groups of mice. When mice were stratified by FI score, frailty predicted mortality, at least in females. Therefore, the mouse clinical FI provides a valuable tool for evaluating healthspan in mouse models of AD with different lifespans.
阿尔茨海默病（AD）小鼠模型的预期寿命因基因型和性别而异。衰弱评估可以提供一种衡量健康寿命的方法，以促进不同AD模型之间的比较。我们使用经过验证的小鼠衰弱指数（FI）评估工具，来探究3xTg-AD小鼠及其B6129F2野生型（WT）对照在寿命和健康寿命方面的基因型和性别差异。该工具基于一种在人类中常用的方法，通过计算与年龄相关的健康缺陷的积累来量化衰弱程度。个体的缺陷数量除以测量的总数得出一个FI分数，理论上在0到1之间，分数越高表示衰弱程度越高。300 - 600日龄的雄性3xTg-AD小鼠的FI分数（平均FI = 0.21 ± 0.03）高于雄性WT小鼠（平均FI = 0.15 ± 0.01）或雌性3xTg-AD小鼠（平均FI = 0.10 ± 0.01），并且衰弱分数的升高伴随着死亡率的平行增加。衰弱程度随年龄呈指数增长，所有小鼠组中更高的缺陷积累率都增加了死亡风险。当按FI分数对小鼠进行分层时，至少在雌性小鼠中，衰弱程度可预测死亡率。因此，小鼠临床FI为评估不同寿命的AD小鼠模型中的健康寿命提供了一个有价值的工具。
