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

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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.