Excellence in Research of dietary blueberry delays aging and reverses aging-induced physical dysfunctions by regulating PPAR pathway

膳食蓝莓通过调节 PPAR 通路延缓衰老并逆转衰老引起的身体功能障碍的卓越研究

基本信息

  • 批准号:
    2200536
  • 负责人:
  • 金额:
    $ 59.12万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

This study aims to understand how the dietary intake of blueberries, which have been shown to have positive effects on health, might work to do so, particularly with regards to people over 65 years of age. Using mice, the project will focus on blueberry’s anti-aging mechanisms at the level of molecules, cells, and tissues. If the preliminary results hold true in the planned longer-term experiments on mice, then the research may lead to work in humans to promote health and extend lifespan by consuming natural blueberry products. With novel experiments examining molecular pathways that impact muscle and blood vessels, two important ideas will be tested: (1) dietary intake of blueberry can extend a healthy lifespan, even starting from advanced age, and (2) dietary intake of blueberry can delay the normal aging process. In addition to the clear societal benefits of understanding how some types of food work to promote health, this project will also provide in-depth research training to minority students (6 graduate students and 6 undergraduates) at a Historically Black University.While the exact mechanisms underlying the aging process are not well understood, delaying the aging-induced physical dysfunctions and related disease development is an essential and effective strategy to promote healthy aging. The PI recently reported that dietary intake of epicatechin (EC), a bioactive component of various foods, including blueberries, reversed aging-induced skeletal muscle (SkM) dysfunction and promoted the survival rate of aged mice. Rabbiteye blueberries contain the highest EC of all fresh fruits. The project will test the hypothesis that dietary blueberry EC reverses the aging-induced dysfunctions of SkM and vascular endothelium by regulating PPAR/NF-kB pathways in aged mice. Two primary objectives structure the experimental work. Objective 1: Test the effects of dietary blueberry and EC in a dose-dependent lifespan protocol. Freeze-dried powders of rabbiteye blueberry (high EC), highbush blueberry (low EC), or pure EC will be administrated to 20-month-old C57BL/6 mice (7 groups, 30 male, 30 female mice/group) until the natural end of lifespan. Complete Kaplan-Meier survival curves and DNA methylation clocks will be used to monitor the aging process. Objective 2: Test that PPAR/NF-kB pathways mediate blueberry EC anti-aging effect in skeletal muscle and vasculature. The whole powder of rabbiteye blueberry, pure EC with/out PPAR specific antagonist GW9662, will be fed to 20-month-old mice for 15 weeks while treadmill performance and ex vivo assays are conducted in parallel. Tissues including SkM, aorta, and serum and in vitro cultured cells will be used to determine the roles of PPAR/NF-kB pathways and other mechanisms of the anti-aging effect by conducting transcriptome and metabolome analyses. As an experimental study of the impact of diet on biochemical pathways, this study will help advance the methodologies for this type of human-health research, in general, and to establish, in particular, the mechanisms by which blueberry intake delays aging-induced dysfunction of skeletal muscle and vasculature and then extends the lifespan in humans.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.
这项研究旨在了解蓝莓的饮食摄入量如何对健康产生积极影响,特别是对于65岁以上的人。利用小鼠,该项目将集中在蓝莓的抗衰老机制在分子,细胞和组织的水平。如果初步结果在计划中的长期小鼠实验中成立,那么这项研究可能会导致人类通过食用天然蓝莓产品来促进健康和延长寿命。通过研究影响肌肉和血管的分子途径的新实验,将测试两个重要的想法:(1)蓝莓的饮食摄入可以延长健康的寿命,即使从高龄开始,(2)蓝莓的饮食摄入可以延缓正常的衰老过程。除了了解某些类型的食物如何促进健康的明显社会效益外,该项目还将为少数民族学生提供深入的研究培训(6名研究生和6名本科生)在一所历史悠久的黑人大学。虽然衰老过程的确切机制还不清楚,延缓衰老引起的身体功能障碍和相关疾病的发展是促进健康老龄化的重要和有效的策略。PI最近报道,膳食摄入表儿茶素(EC),包括蓝莓在内的各种食物的生物活性成分,逆转了衰老诱导的骨骼肌(SkM)功能障碍,并提高了老年小鼠的存活率。兔眼蓝莓含有所有新鲜水果中最高的EC。该项目将测试以下假设:膳食蓝莓EC通过调节老年小鼠中的PPAR/NF-kB通路来逆转衰老诱导的SkM和血管内皮功能障碍。实验工作有两个主要目标。目的1:以剂量依赖性寿命方案测试膳食蓝莓和EC的影响。将兔眼蓝莓(高EC)、高丛蓝莓(低EC)或纯EC的冻干粉给予20个月大的C57 BL/6小鼠(7组,30只雄性,30只雌性小鼠/组),直至寿命自然结束。完整的Kaplan-Meier生存曲线和DNA甲基化时钟将用于监测老化过程。目的2:检测蓝莓EC抗骨骼肌和血管衰老作用是否通过PPAR/NF-kB通路介导。将兔眼蓝莓的全粉(不含/不含PPAR特异性拮抗剂GW 9662的纯EC)饲喂20月龄小鼠15周,同时平行进行跑步机性能和离体测定。包括SkM、主动脉和血清在内的组织以及体外培养的细胞将用于通过进行转录组和代谢组分析来确定PPAR/NF-kB通路的作用以及抗衰老作用的其他机制。作为饮食对生化途径影响的实验研究,这项研究将有助于推进这类人类健康研究的方法,特别是建立,蓝莓摄入延缓衰老的机制诱发骨骼肌和脉管系统的功能障碍,然后延长人类的寿命。该奖项反映了NSF的法定使命,并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

项目成果

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Hongwei Si其他文献

Absolute phase synchronization over optical fiber
光纤绝对相位同步
  • DOI:
    10.1364/oe.387166
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    Hongwei Si;Bo Wang;Fangmin Wang;Yufeng Chen;Lijun Wang
  • 通讯作者:
    Lijun Wang
Evaluation of the estimated variables for scaling glomerular filtration rate of renal patients: A repeated measures-based method
评估肾病患者肾小球滤过率的估计变量:基于重复测量的方法
Regressing an Optimal Variable to Scale Glomerular Filtration Rate: More Variations in Glomerular Filtration Rate Are Explained
回归最佳变量来衡量肾小球滤过率:解释了肾小球滤过率的更多变化
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    10.6
  • 作者:
    Hongwei Si;Yingmao Chen;M. Shao;Guangyu Ma;Baixuan Xu;Tian Jiahe;Chen Yunshuang;Xuefeng Sun
  • 通讯作者:
    Xuefeng Sun
The dynamic scale modeling of
动态尺度建模
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hongwei Si;Dongxu Li
  • 通讯作者:
    Dongxu Li
Combination of curcumin and luteolin synergistically inhibits TNF-α-induced vascular inflammation in human vascular cells and mice.
姜黄素和木犀草素的组合可协同抑制人血管细胞和小鼠中 TNF-α 诱导的血管炎症。
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Lijuan Zhang;Xiaoyong Wang;Longyun Zhang;C. Virgous;Hongwei Si
  • 通讯作者:
    Hongwei Si

Hongwei Si的其他文献

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