Mechanisms of Lifespan Modulation by Diet

饮食调节寿命的机制

• 批准号: 8736539
• 负责人: Sige Zou
• 金额: $ 60.46万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8736539
• 关键词: Accounting; Address; Age; Aging; Aging-Related Process; Anastrepha ludens; Animal Model; Behavior; Behavior monitoring; Behavioral; Biological Preservation; Biological Sciences; Collaborations; Cranberries; Custom; Data; Demographic Aging; Diet; Drosophila genus; Environmental Risk Factor; Equilibrium; Fatty acid glycerol esters; Foundations; Future; Genes; Genetic; Gerontology; Goals; Health Benefit; Human; Intake; Intervention; Intervention Studies; Invertebrates; Journals; Light; Longevity; Macronutrients Nutrition; Measures; Medicine; Mexico; Mission; Modeling; Molecular; Motor Activity; National Institute on Aging; Nutraceutical; Nutrient; Organism; Output; Pharmacologic Substance; Phytochemical; Plants; Population; Protein-Restricted Diet; Proteins; Publications; Publishing; Reporting; Research; Resolution; Role; Sleep; Supplementation; System; Time; Work; age effect; age related; anti aging; biological adaptation to stress; cellular longevity; effective intervention; feeding; fly; functional genomics; genetic resource; healthy aging; improved; intervention effect; reproductive; sugar; tool

Aging is modulated by both genetic and environmental factors. Dietary nutrients have been shown to be among the most potent environmental factors that have significant impact on healthspan and lifespan. A number of pharmaceuticals and nutraceuticals have been identified to have prolongevity effects in model organisms. Nutraceuticals made from plants are rich in phytochemicals, which possess diverse bioactivities and exert numerous health benefits, including anti-aging effects. However, whether and how dietary nutrients influence the prolongevity effects of interventions for promoting healthy aging remains elusive. This is an important issue in the aging field to address considering diverse dietary customs among human populations of different geographic origins. Invertebrates including worms and flies are ideal model organisms to investigate the prolongevity effect of pharmaceuticals and nutraceuticals at least partially due to their short lifespan and rich genetic resources. We have summarized the research progress on prolongevity nutraceuticals using invertebrate models and published a review in Oxidative Medicine and Cellular Longevity (2013). This work should provide valuable guidance for future mechanistic studies on the effect of nutraceutical supplementation in delaying aging process and improve healthspan. To investigate the interaction between nutraceuticals and macronutrients in lifespan modulation, we have investigated the effect of cranberry-derived nutraceuticals on lifespan and determined the impact of dietary macronutrient composition on the prolongevity effect of cranberry in Drosophila. We have found that cranberry can extend lifespan of flies fed a diet with modest amount of sugar and protein, and increase lifespan more prominently in flies fed a high sugar-low protein diet, but does not extend or shorten lifespan of flies fed a low sugar-high protein diet. We have further demonstrated that lifespan extension induced by cranberry supplementation is associated with increased lifetime reproductive output and higher expression of stress response genes. We have also shown that cranberry can improve the survival of flies fed a high-fat diet. This study reveals the critical role of dietary macronutrients in the prolongevity effect of cranberry supplementation and points out the importance of take into account diet composition in implementing interventions for promoting healthy aging. This line of the work has been accepted for publication in Journal of Gerontology Biological Sciences (2013). Future work will be directed more to understand the molecular mechanisms underlying the prolongevity effect of cranberry supplementation and its interaction between dietary macronutrients in modulating lifespan. This will provide a comprehensive view of and help improve interventions for promoting healthy aging. An important issue in aging studies is to assess healthspan since a fundamental goal of aging research is to not just increase lifespan but significantly improve healthspan through the preservation of function. Aging is associated with numerous behavioral changes, such as gradual decline of locomotor activity, which is a parameter for healthspan. Many tools are available for measuring locomotor activity in model organisms and humans. However, age-related behavioral changes remain poorly understood mainly due to the lack of tools capable of recording lifelong behavioral changes in a high resolution in any organism. We have previously developed a behavior monitor system (BMS) that can record six types of behaviors in a fine resolution over the lifetime of Mexican fruit flies (mexflies). Mexflies have been used extensively in demographic and aging intervention studies. In collaboration with Drs. Pablo Liedo at Mexico, Joanne Chiu and James Carey at UC Davis and Donald Ingram at Pennington, we have taken advantage of the BMS to investigate the impact of diet on age-related changes in locomotor activity, sleep quantity and quality using the high resolution lifelong behavior recording data in mexflies. We have found that flies under a nutritionally balanced diet have little age-related change in activity profile, while flies on suboptimal diet have a significant decrease of activity in amplitude and lower sleep quality at old age. This line of work has been published in Scientific Reports (2013). Future work will be to use the BMS to evaluate lifelong behavioral changes induced by any prolongevity interventions to shed light on the impact of aging interventions on healthspan. We will also develop a similar BMS for Drosophila in order to investigating molecular mechanisms underlying the lifelong behavioral changes. In summary, we have determined the impact of dietary macronutrients on the prolongevity effect of a cranberry-containing nutraceutical in Drosophila. We have assessed the impact of diet on healthspan by analyzing lifelong behavioral changes in mexflies under different dietary conditions. These findings provide the foundation for our future research directed towards understanding the molecular mechanisms underlying the interplay between dietary macronutrients and nutraceuticals or pharmaceuticals in modulating lifespan and healthspan. These studies should provide valuable information for developing efficient interventions for promoting healthy aging in humans. This project should advance the objectives of the Translational Gerontology Branch and overall missions of the National Institute on Aging.

衰老受遗传和环境因素的影响。饮食营养素已被证明是对健康和寿命有重大影响的最有力的环境因素之一。许多药物和营养食品已被确定在模式生物中具有延长寿命的作用。由植物制成的营养食品含有丰富的植物化学物质，具有多种生物活性，对健康有许多好处，包括抗衰老作用。然而，饮食营养是否以及如何影响促进健康老龄化的干预措施的长寿效果仍然难以捉摸。考虑到不同地理来源的人群之间不同的饮食习惯，这是老龄化领域需要解决的一个重要问题。包括蠕虫和苍蝇在内的无脊椎动物是研究药物和营养食品延寿效应的理想模式生物，至少部分原因是它们的寿命短，遗传资源丰富。我们总结了利用无脊椎动物模型研究延寿营养食品的进展，并发表了一篇综述，发表在《氧化医学和细胞寿命》(2013)上。这项工作将为今后营养补充剂延缓衰老进程和提高健康寿命的作用机制研究提供有价值的指导。 为了探讨营养食品与常量营养素在延寿过程中的相互作用，我们研究了蔓越莓源营养素对果蝇寿命的影响，并确定了饲料中常量营养素组成对果蝇蔓越莓延寿效应的影响。我们发现，小红莓可以延长喂食适量糖分和蛋白质食物的果蝇的寿命，并且在喂食高糖低蛋白质食物的果蝇中寿命延长得更明显，但不能延长或缩短喂食低糖高蛋白食物的果蝇的寿命。我们进一步证明，补充小红莓导致的寿命延长与增加生命的生殖输出和更高的应激反应基因的表达有关。我们还表明，小红莓可以提高喂食高脂肪食物的果蝇的存活率。本研究揭示了膳食中大量营养素在补充小红莓延年益寿中的关键作用，并指出了在实施促进健康老龄化的干预措施中考虑膳食结构的重要性。这项工作已被《老年学生物科学杂志》(2013)接受发表。未来的工作将更多地致力于了解蔓越莓补充剂延长寿命的分子机制，以及它在调节寿命中饮食中大量营养素之间的相互作用。这将提供一个全面的视角，并有助于改进促进健康老龄化的干预措施。 老龄化研究中的一个重要问题是评估健康寿命，因为衰老研究的一个基本目标不仅是延长寿命，而且通过保留功能来显着提高健康寿命。衰老与许多行为变化有关，例如运动活动逐渐减少，这是健康寿命的一个参数。有许多工具可以用来测量模型生物和人类的运动活动。然而，与年龄相关的行为变化仍然知之甚少，这主要是因为缺乏能够在任何生物体中以高分辨率记录终身行为变化的工具。我们之前已经开发了一种行为监测系统(BMS)，可以在墨西哥果蝇(墨西哥果蝇)的一生中以精细的分辨率记录六种类型的行为。墨西哥苍蝇已被广泛用于人口统计学和老龄化干预研究。与墨西哥的Pablo Liedo博士、加州大学戴维斯分校的Joanne Chiu和James Carey以及Pennington的Donald Ingram合作，我们利用BMS的优势，使用高分辨率的麦克斯苍蝇终身行为记录数据，研究了饮食对运动活动、睡眠数量和质量的年龄相关变化的影响。我们发现，营养均衡饮食的果蝇活动谱随年龄的变化很小，而营养均衡饮食的果蝇在老年时活动幅度显著下降，睡眠质量下降。这项工作已发表在《科学报告》(2013)上。未来的工作将是使用BMS来评估任何延寿干预引起的终身行为变化，以阐明老龄化干预对健康寿命的影响。我们还将为果蝇开发类似的BMS，以研究导致终生行为变化的分子机制。 综上所述，我们已经确定了饮食中的大量营养素对含有红莓的营养食品在果蝇中的延长效果的影响。我们通过分析不同饮食条件下苍蝇终身行为的变化，评估了饮食对健康寿命的影响。这些发现为我们未来的研究奠定了基础，这些研究旨在了解膳食中大量营养素与营养食品或药物在调节寿命和健康方面相互作用的分子机制。这些研究应该为开发有效的干预措施来促进人类的健康老龄化提供有价值的信息。该项目应推进翻译老年学分部的目标和国家老龄问题研究所的总体任务。