Doctoral Dissertation Research: Investigating the relationship between diet and biological age with a primate epigenetic clock

博士论文研究：利用灵长类表观遗传时钟研究饮食与生物年龄之间的关系

• 批准号: 1920350
• 负责人: Kirstin Sterner
• 金额: $ 2.94万
• 依托单位: University of Oregon Eugene
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1920350&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Investigating; relationship

Unlike chronological age (the number of years a person has lived), biological age accounts for environmental, genetic and lifestyle factors that influence the pace of age-related changes. Diet is thought to be one such factor; however, the relationship between diet and biological aging is not well understood, and efforts to characterize this relationship have struggled to disentangle the effects of diet from other variables. This doctoral dissertation project will examine the effect of diet on the rate of biological aging using a newly developed epigenetic clock, a biomarker of biological age. This fundamental research will advance knowledge about human biology, life history, and senescence. The project may also inform public health and aging research by quantifying how lifestyle factors like diet "get under the skin" to influence the aging process and age-related disease. In addition, this project will contribute to the education, training and professional development of a female graduate student in a STEM field, and will include science outreach and education activities to engage with K-12 and public audiences.The mechanisms that regulate the rate of biological aging are unknown but may have origins in the epigenome, a collection of chemical modifications to DNA that influence how genes are turned on or off. The epigenome is able to connect environment to genetics, and therefore plays a key role in explaining how environment and lifestyle factors can shape the pace of biological aging at the molecular level. Recently, age predictor models called epigenetic clocks have been developed that use age-associated changes in the epigenome to generate estimates of biological age. These clocks can be used to study the phenomenon of accelerated aging, where biological age exceeds chronological age. This project will construct a multi-tissue epigenetic clock and use this clock to test the effect of diet on biological age in a non-human primate model. The central hypothesis of this research is that an obesogenic diet accelerates biological aging and caloric restriction slows biological aging. The researchers will collect and analyze genome-wide methylation data from banked liver samples using reduced representation bisulfite sequencing (RRBS) and combine these data with previously collected RRBS data from blood samples. A comparative non-human primate model with similar life history and disease risk can provide important insights into human aging.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

与时序年龄(一个人的寿命)不同，生物年龄考虑了环境、遗传和生活方式因素，这些因素会影响与年龄相关的变化速度。饮食被认为是其中一个因素；然而，饮食和生物衰老之间的关系还没有被很好地理解，而且努力描述这种关系的努力一直在努力将饮食的影响从其他变量中分离出来。这个博士论文项目将使用一种新开发的表观遗传学时钟来研究饮食对生物衰老速度的影响，表观遗传时钟是生物年龄的生物标记物。这项基础性研究将促进对人类生物学、生活史和衰老的了解。该项目还可能通过量化饮食等生活方式因素如何影响衰老过程和与年龄相关的疾病，为公共健康和老龄化研究提供信息。此外，该项目将有助于STEM领域女研究生的教育、培训和专业发展，并将包括与K-12和公众接触的科学推广和教育活动。调节生物衰老速度的机制尚不清楚，但可能起源于表观基因组，即对DNA的化学修饰的集合，影响基因的开启或关闭。表观基因组能够将环境和遗传学联系起来，因此在解释环境和生活方式因素如何在分子水平上塑造生物衰老速度方面发挥了关键作用。最近，被称为表观遗传时钟的年龄预测模型已经开发出来，它使用表观基因组中与年龄相关的变化来产生生物年龄的估计。这些时钟可以用来研究生物年龄超过实际年龄的加速衰老现象。该项目将构建一个多组织表观遗传学时钟，并使用该时钟在非人类灵长类动物模型中测试饮食对生物年龄的影响。这项研究的中心假设是，肥胖饮食会加速生物衰老，而限制卡路里摄入会减缓生物衰老。研究人员将使用简化代表性亚硫酸氢盐测序(RRBS)收集和分析银行肝脏样本的全基因组甲基化数据，并将这些数据与之前从血液样本收集的RRBS数据结合起来。具有相似生活史和疾病风险的比较非人类灵长类动物模型可以为人类衰老提供重要的见解。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。