Waters David J, Maras Aimee H, Fu Rong, Carrillo Andres E, Chiang Emily C, Suckow Cheri L
Center for Exceptional Longevity Studies, Gerald P. Murphy Cancer Foundation, West Lafayette, IN 47906, USA.
Center on Aging and the Life Course and the Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN 47907, USA.
Animals (Basel). 2024 Dec 18;14(24):3651. doi: 10.3390/ani14243651.
Frailty refers to a state of increased vulnerability to mortality and other adverse outcomes as a consequence of age-related decline in physiologic reserve and function. Comparative biomedical scientists are relied upon to innovate approaches to enhance understanding of the similarities and differences between humans and other animal species that can impact healthy aging. The research aim of this study was to develop a clinical frailty index (FI) in the Exceptional Aging in Rottweilers Study (EARS) and test its ability to predict all-cause mortality in elderly dogs. EARS is an ongoing lifetime cohort study of pet dogs with extreme longevity living in North America. Living 30% longer than the breed average, these dogs represent the canine counterpart to human centenarians. A 34-item FI (EARS-FI) was constructed to assess deficit accumulation using clinical data collected by telephone interviews with owners of 93 dogs with extreme longevity. Health deficits across multiple domains, including cognitive and sensory, cardiovascular and endocrine, and mobility, were included. The association between EARS-FI and subsequent mortality was tested in Kaplan-Meier survival analysis and in age-adjusted Cox proportional hazard models. Median (interquartile range) EARS-FI was 0.43 (0.38-0.50), and the estimated frailty limit was 0.68, consistent with data reported in humans with extreme longevity. Frailty index increased with increasing chronological age ( < 0.001). Deficit accumulation was significantly associated with increased mortality risk. Age-adjusted hazard ratio for mortality per 0.01 unit increase in FI was 1.05 (95%CI, 1.02-1.08; = 0.001). This work provides the first demonstration of a strong association between frailty and mortality risk in pet dogs with extreme longevity. Notably, EARS-FI showed key features observed in the evaluation of frailty in aging human populations: heterogeneity, increase with chronological age, and estimated limit of <0.7. Validated here as a predictor of mortality in aged pet dogs, EARS-FI offers a useful tool for further comparative analyses of the linkages between deficit accumulation, mortality, and other adverse health outcomes.
衰弱是指由于生理储备和功能的年龄相关性下降，导致对死亡和其他不良后果的易感性增加的一种状态。比较生物医学科学家依靠创新方法来增进对人类和其他动物物种之间异同的理解，这些异同可能影响健康老龄化。本研究的目的是在罗威纳犬超常衰老研究（EARS）中开发一种临床衰弱指数（FI），并测试其预测老年犬全因死亡率的能力。EARS是一项正在进行的对生活在北美的极端长寿宠物犬的终生队列研究。这些犬的寿命比该品种平均寿命长30%，它们相当于人类中的百岁老人。构建了一个包含34个条目的FI（EARS-FI），使用通过电话访谈93只极端长寿犬的主人收集的临床数据来评估缺陷积累情况。纳入了多个领域的健康缺陷，包括认知和感官、心血管和内分泌以及活动能力等方面。在Kaplan-Meier生存分析和年龄调整的Cox比例风险模型中测试了EARS-FI与随后死亡率之间的关联。EARS-FI的中位数（四分位间距）为0.43（0.38 - 0.50），估计的衰弱界限为0.68，这与关于极端长寿人类的数据一致。衰弱指数随实际年龄增加而升高（<0.001）。缺陷积累与死亡风险增加显著相关。FI每增加0.01单位，年龄调整后的死亡风险比为1.05（95%CI，1.02 - 1.08； = 0.001）。这项工作首次证明了在极端长寿的宠物犬中，衰弱与死亡风险之间存在强关联。值得注意的是，EARS-FI显示出在评估老年人群衰弱时观察到的关键特征：异质性、随实际年龄增加以及估计界限<0.7。EARS-FI在此被验证为老年宠物犬死亡率的预测指标，它为进一步比较分析缺陷积累、死亡率和其他不良健康结局之间的联系提供了一个有用的工具。
