Measurements of telomere length at different life stages as predictive biomarkers of health, reproduction and longevity in dairy cattle

拟议工作的关键概念基于三个原则：1。健康、繁殖和寿命是影响英国和国际畜牧业可持续性和盈利能力的关键因素。除了具有相当大的经济意义外，这些因素还影响动物福利、畜牧业的环境足迹以及消费者对动物产品的接受程度。因此，这些性状的改良将产生多方面的效益。考虑到影响准确记录这些特征的复杂性和时间要求，需要可靠的早期生命预测器，可以为健康状况不佳、生殖和寿命不长提供早期预警，有效地为改善提供实用工具。人类和实验动物研究的最新进展揭示了与寿命以及年龄和年龄相关疾病相关的潜在有用的生物标志物。拟议的项目旨在确定一种早期生命生物标志物，以预测奶牛的健康，繁殖和寿命。出于这个原因，该项目将使用苏格兰克莱顿皇家农场实验牛群饲养的奶牛的综合数据库。动物属于两个不同的遗传系（选择高产量与平均产量）和两个饮食组（高蛋白质摄入量与低蛋白质摄入量），从出生到死亡或从牛群中移除都受到密切监测。该数据库包括个体动物谱系、性能、采食量、疾病和生殖事件以及寿命的记录。与这些记录相关的详细环境描述也包括在数据库中。该畜群中约有1 000头动物在出生时和每6个月进行一次血液采样。这些样本将用于测量每头奶牛一生中端粒的长度。端粒是动物细胞中覆盖染色体末端的小结构，已知与人类衰老有关。将在动物的整个生命周期内监测拟定研究中获得的端粒长度测量值的变化，并与健康事件、生殖问题和生产寿命长度相关的数据一起进行分析。这些分析将建立动物端粒长度与健康、生殖和寿命之间的联系。为了实现其目标，该项目将借鉴动物科学、遗传学、生物技术、生理学和生物学方面的互补专业知识。这是有史以来第一次对食用动物进行研究，研究端粒随时间变化的方式，以及这种变化如何与重要的动物性状相关。此外，许多遗传和环境因素对端粒和寿命的影响也将首次得到研究。该项目的成果将使人们更好地了解产奶奶牛的衰老过程，并将确定一个早期生命指标，预测动物未来的健康、繁殖和寿命。3.最终结果将是一种易于应用的动物友好型生物标志物，可用作管理和选择工具，以提高奶牛的健壮性，福利和存活率，并降低高产动物从牛群中非自愿移除的比率。设想的改进的进一步后果包括动物产品的生产和消费更健康的背景，以及整个行业的环境足迹更低。4.在这个项目中获得的知识可能对动物保护计划产生更深远的影响，以改善稀有动物品种和濒危物种的生存，以及详细的研究，以更好地了解包括人类在内的其他物种的衰老过程。

The key concept of the proposed work is based on three tenets:1. Health, reproduction and longevity are key factors influencing the sustainability and profitability of the livestock industry in the UK and internationally. In addition to bearing considerable economic significance, these factors affect animal welfare, the environmental footprint of livestock operations, and the acceptability of animal products by consumers. Therefore, improvement of these traits will yield multi-faceted benefits.2. Given the complexities and time requirements affecting the accurate recording of these traits, there is a need for reliable, early-life predictors that could provide early warnings for poor health, reproduction and longevity, effectively contributing practical tools for improvement.3. Recent advances in human and laboratory animal research have revealed potentially useful biological markers that are associated with lifespan, as well as age and age-related conditions.The proposed project aims to identify an early-life biomarker to predict health, reproduction and longevity in dairy cattle. For this reason, the project will use a comprehensive database of cows raised in the experimental herd of the Crichton Royal Farm in Scotland. Animals belong to two different genetic lines (selected for high vs. average production) and two diet groups (high vs. low protein intake) and are closely monitored from the time of birth until they die or are removed from the herd. The database comprises records of individual animal pedigree, performance, feed intake, disease and reproductive events, and longevity. Detailed environmental descriptors associated with these records are also included in the database.Approximately 1,000 animals from this herd have already been blood sampled at birth and then in 6-month intervals. These samples will be used to measure the length of the telomeres of each cow across her lifetime. Telomeres are small structures capping the chromosomes' ends in the animal cells and are known to be associated with aging in humans. Changes in telomere length measures obtained in the proposed study will be monitored throughout the animals' life and analysed together with data pertaining to health events, reproductive issues and length of productive life. These analyses will establish the link between animal telomere length and health, reproduction and longevity.To achieve its objectives, the project will draw on complementary expertise in animal science, genetics, biotechnology, physiology and biology.The potential applications and benefits of this study are as follows:1. This is the first ever study in food producing animals that looks at the way telomeres change across time and how this change may relate to important animal traits. Also for the first time the effect of many genetic and environmental factors on telomeres and longevity will be examined.2. The outcome of the project will bring a better understanding of the process of ageing of milk producing cows and will identify an early-life indicator that predicts the animals' future health, reproduction and longevity. 3. The end result will be an easily applicable, animal-friendly biomarker that could be used as a management and selection tool to improve the robustness, welfare and survival of dairy cattle, and reduce the rate of involuntary removal of high yielding animals from the herds. Further ramifications of the envisaged improvement include a healthier background for the production and consumption of animal products, and a lower environmental footprint of the sector as a whole. 4. Knowledge acquired in this project may have longer reaching consequences for animal conservation programmes to improve survival of rare animal breeds and endangered species, as well as detailed studies to better understand the aging process in other species including humans.