Herzig Sébastien, Zollinger Alix, Texari Lorane, Holzwarth James A, Middleton Rondo P, Pan Yuanlong, Steiner Pascal, Gut Philipp
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
Nestlé Institute of Food Safety and Analytical Sciences, Nestlé Research, Lausanne, Switzerland.
Geroscience. 2025 Feb;47(1):45-59. doi: 10.1007/s11357-024-01352-4. Epub 2024 Oct 1.
Predicting aging trajectories through biomarkers of biological aging can guide interventions that optimize healthy lifespan in humans and companion animals. Differences in physiology, genetics, nutrition, and lifestyle limit the generalization of such biomarkers and may therefore require species-specific algorithms. Here, we compared correlations of standard clinical blood parameters with survival probability in humans with those of the two most common mammalian companion animals, cats and dogs, and highlighted universal and species-specific relationships. Based on this comparative analysis, we generated and validated an algorithm that predicts biological age in canines using a longitudinal dataset with health records, blood count, and clinical chemistry from 829 dogs spanning over 12 years. Positive deviations of biological from chronological age (AgeDev) measured by this composite score significantly correlated with a decreased survival probability (hazard ratio = 1.75 per 1 year of AgeDev, p = 3.7e - 06). Importantly, in nearly half of the dogs whose biological age was accelerated by more than 1 year, none or only a single individual marker scored outside its respective reference range, suggesting practical applications for the detection of unfavorable health trajectories. Analyzing samples from a unique 14-year life-long diet restriction study, we show that restricted caloric intake lowers biological age, an effect that can be quantified at midlife years before a difference in survival is observed. Thus, a biological age clock based on clinical blood tests predicts the health trajectories of dogs for use in research and veterinary practice.
通过生物衰老的生物标志物预测衰老轨迹,可以指导优化人类和伴侣动物健康寿命的干预措施。生理、遗传、营养和生活方式的差异限制了此类生物标志物的通用性,因此可能需要特定物种的算法。在这里,我们比较了人类标准临床血液参数与生存概率之间的相关性,以及两种最常见的哺乳动物伴侣动物猫和狗的相应相关性,并突出了通用和特定物种的关系。基于这种比较分析,我们生成并验证了一种算法,该算法使用一个包含829只狗超过12年的健康记录、血细胞计数和临床化学的纵向数据集来预测犬类的生物年龄。通过这个综合评分测量的生物年龄与实际年龄的正向偏差(年龄偏差)与生存概率降低显著相关(年龄偏差每增加1年,风险比=1.75,p=3.7e-06)。重要的是,在近一半生物年龄加速超过1年的狗中,没有或只有一个个体标志物超出其各自的参考范围,这表明该算法在检测不良健康轨迹方面具有实际应用价值。通过分析一项独特的为期14年的终身饮食限制研究的样本,我们发现热量摄入受限会降低生物年龄,这种影响在观察到生存差异之前的中年时期就可以量化。因此,基于临床血液检测的生物年龄时钟可以预测狗的健康轨迹,用于研究和兽医实践。