Nutritional and Epigenetic Priming of Metabolism and Aging in Drosophila

描述（由申请人提供）：在生长和发育的重要时期，动物对其营养环境高度敏感，可以改变其代谢，导致终生持续的变化。生命早期的营养不良会导致适应不良，从而增加患2型糖尿病和心脏病等代谢紊乱的风险。最近的研究表明，早期营养暴露也可能直接影响寿命和与衰老相关的细胞过程。然而，由于纵向动物研究的昂贵性，很难比较不同年龄组的不同饮食暴露的影响。此外，早期饮食对新陈代谢和衰老的影响的细胞机制在很大程度上尚未探索。该应用建立了一个使用果蝇（Drosophila melanogaster）的新平台，以研究早期营养对寿命和整体健康的作用。拟议的目标将剖析基本的表观遗传机制和生理变化的基础上的营养不良的影响，在关键时期的发展代谢老化。这些研究将为药物干预提供新的策略和遗传靶点，以扭转早期不良饮食的影响，并可能改善人类健康状况。

DESCRIPTION (provided by applicant): During important periods of growth and development, animals are highly sensitive to their nutritional environment and can modify their metabolism, causing changes that persist throughout life. Poor nutrition early in life can lead to maladaptations that later increase the risk of metabolic disorders such as type 2 diabetes and heart disease. Recent studies indicate that early nutritional exposures may also directly affect longevity and cellular processes associated with aging. However, due to the costly nature of longitudinal animal studies, it is difficult to compare the effects of diverse dietary exposures an age groups. In addition, the cellular mechanisms underlying the effects of early diet on metabolism and aging are largely unexplored. This application establishes a novel platform using the fruit fly, Drosophila melanogaster, to investigate the role of early nutrition on lifespa and overall health. The proposed aims will dissect the fundamental epigenetic mechanisms and physiological changes that underlie the effects of poor nutrition during critical periods of development on metabolic aging. These studies will provide new strategies and genetic targets for pharmacological interventions that reverse the effects of poor early diet and potentially improve human healthspan.