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.

与年龄年龄（一个人寿命的年龄）不同，生物年龄涉及影响与年龄相关变化速度的环境，遗传和生活方式因素。饮食被认为是这样的因素之一。但是，饮食与生物衰老之间的关系尚不清楚，并且为这种关系而努力的努力努力将饮食的影响与其他变量相关。该博士学位论文项目将使用新开发的表观遗传时钟（生物年龄的生物标志物）研究饮食对生物衰老率的影响。这项基本研究将促进有关人类生物学，生活史和衰老的知识。该项目还可以通过量化饮食等生活方式因素如何“陷入皮肤”以影响衰老过程和与年龄有关的疾病，从而为公共卫生和老龄化研究提供依据。此外，该项目将有助于STEM领域的女性研究生的教育，培训和专业发展，并包括科学外展和教育活动，与K-12和公众受众互动。调节生物衰老速率的机制尚不清楚，但可能起源于表观镜头，对dna的收集到对基因的DNA收集。表观基因组能够将环境与遗传学联系起来，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的速度方面起着关键作用。最近，已经开发出了称为表观遗传时钟的年龄预测模型，该模型使用了与年龄相关的表观基因组的变化来产生生物年龄的估计值。这些时钟可用于研究生物年龄超过年代年龄的加速衰老现象。该项目将构建一个多组织的表观遗传时钟，并使用此时钟来测试非人类灵长类动物模型中饮食对生物年龄的影响。这项研究的核心假设是，肥胖饮食会加速生物衰老和热量限制，这减慢了生物衰老。研究人员将使用降低的代表性亚硫酸盐测序（RRB）收集和分析来自银行肝样品的全基因组甲基化数据，并将这些数据与先前从血液样本中收集的RRB数据相结合。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。该奖项反映了NSF的法定任务，并认为使用基金会的知识分子优点和更广泛的影响评估标准，被认为值得通过评估。