Agricultural Research Organization, Volcani Center, Institute of Animal Science, Rishon LeZion, Israel.
Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot,Israel.
J Gerontol A Biol Sci Med Sci. 2021 Sep 13;76(10):1757-1768. doi: 10.1093/gerona/glab135.
Aging in vertebrates is an extremely complex process that is still poorly understood. One confining factor to studying vertebrate aging is the lack of appropriate models. The laying hen is a good model to study vertebrate aging, as it can be maintained under standard housing conditions, its breeds are genetically well defined and it exhibits significant aging phenotypes at around 18 months of age. Furthermore, laying hens are maintained in a challenging realistic environment and possess a fully functional immune system. Here we used, for the first time, metabolomic profiling of laying hens' blood for identifying biomarkers of aging. Random forest classifier was used to quantify the quality of the markers and found that the markers can predict the correct age group of individuals with 90% accuracy. Animals under time-restricted feeding, a condition known to increase health span, appeared younger under the markers, indicating that the aging biomarkers can also predict the effectiveness of environmental treatments. Additionally, we found that noise, defined as the ratio between the standard deviation and the mean, is an exceptionally robust and universal biomarker of aging, as metabolomic noise increases significantly with age in laying hens, humans, and mice. Our study suggests the laying hen as a useful model to study aging in vertebrates and establishes metabolomic noise as a novel, universal biomarker of aging.
脊椎动物的衰老过程极其复杂,目前仍知之甚少。研究脊椎动物衰老的一个限制因素是缺乏合适的模型。产蛋母鸡是研究脊椎动物衰老的一个很好的模型,因为它可以在标准的饲养条件下维持,其品种在遗传上定义明确,并且在大约 18 个月大时表现出明显的衰老表型。此外,产蛋母鸡在具有挑战性的现实环境中饲养,拥有功能齐全的免疫系统。在这里,我们首次使用代谢组学方法对产蛋母鸡的血液进行分析,以鉴定衰老的生物标志物。随机森林分类器用于量化标志物的质量,发现这些标志物可以以 90%的准确率预测个体的正确年龄组。在限时喂养条件下,即已知可以增加健康跨度的条件下,动物看起来更年轻,这表明衰老生物标志物也可以预测环境处理的效果。此外,我们发现,噪声(定义为标准差与平均值的比值)是衰老的一个非常稳健和普遍的生物标志物,因为在产蛋母鸡、人类和老鼠中,代谢组噪声随着年龄的增长显著增加。我们的研究表明,产蛋母鸡是研究脊椎动物衰老的有用模型,并确立了代谢组噪声作为一种新的、普遍的衰老生物标志物。