Institute of Animal Science, Department of Poultry and Aquaculture, Agricultural Research Organization, Volcani Center, Rishon LeZion, Israel.
The Mina and Everard Goodman Faculty of Life Sciences, The Sagol Center for Healthy Human Longevity, Bar-Ilan University, Ramat Gan, Israel.
Geroscience. 2024 Apr;46(2):2343-2358. doi: 10.1007/s11357-023-00969-1. Epub 2023 Nov 10.
Among land vertebrates, the laying hen stands out due to its great reproductive efficiency: producing an egg daily all year long. This production rate makes the laying hen a special model animal to study the general process of reproduction and aging. One unique aspect of hens is their ability to undergo reproductive plasticity and to rejuvenate their reproductive tract during molting, a standard industrial feed restriction protocol for transiently pausing reproduction, followed by improved laying efficiency almost to peak production. Here we use longitudinal metabolomics, immunology, and physiological assays to show that molting promotes reproduction, compresses morbidity, and restores youthfulness when applied to old hens. We identified circulating metabolic biomarkers that quantitatively predict the reproduction and age of individuals. Lastly, we introduce metabolic noise, a robust, unitless, and quantifiable measure for heterogeneity of the complete metabolome as a general marker that can indicate the rate of aging of a population. Indeed, metabolic noise increased with age in control hens, whereas molted hens exhibited reduced noise following molting, indicating systemic rejuvenation. Our results suggest that metabolic noise can be used as a quick and universal proxy for assessing successful aging treatments, accelerating the timeline for drug development.
在陆地脊椎动物中，蛋鸡因其极高的繁殖效率而脱颖而出：全年每天产一个蛋。这种高生产率使蛋鸡成为研究生殖和衰老一般过程的特殊模式动物。母鸡的一个独特之处是它们具有生殖可塑性的能力，并在换羽期间使生殖道再生，换羽是一种标准的工业饲料限制方案，用于暂时停止生殖，随后生殖效率提高，几乎达到最高生产水平。在这里，我们使用纵向代谢组学、免疫学和生理测定来表明，换羽可以促进生殖、压缩发病，并使老年母鸡恢复年轻。我们确定了循环代谢生物标志物，这些生物标志物可以定量预测个体的生殖和年龄。最后，我们引入了代谢噪声，这是一种稳健的、无单位的、可量化的完整代谢组异质性的度量标准，它可以作为一个普遍的指标来指示种群的衰老速度。事实上，在对照组母鸡中，代谢噪声随着年龄的增长而增加，而换羽后的母鸡则表现出代谢噪声降低，这表明全身年轻化。我们的研究结果表明，代谢噪声可用作评估成功的衰老治疗方法的快速且通用的替代指标，从而加速药物开发的时间线。
