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调节。饮食营养素已被证明是对健康范围和寿命产生重大影响的最有效的环境因素之一。已经确定许多药物和营养素在模型生物体中具有延长效果。由植物制成的营养素富含植物化学物质，具有多种生物活性，并具有许多健康益处，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衰老的干预措施的延长效果仍然难以捉摸。这是老化领域的一个重要问题，可以解决不同地理起源人群中各种饮食习俗的解决。包括蠕虫和苍蝇在内的无脊椎动物是理想的模型生物，用于研究药物和营养素的延长效应，至少部分是由于它们的寿命短和丰富的遗传资源。我们总结了使用无脊椎动物模型在Prolongevity Nutraceuticals上的研究进展，并发表了氧化医学和细胞寿命的评论（2013）。这项工作应为未来的机械研究提供宝贵的指导，以延迟衰老过程并改善健康状况。 为了研究寿命调节中营养素与大量营养素之间的相互作用，我们研究了蔓越莓衍生的营养素对寿命的影响，并确定了饮食中大量营养素成分对氯糖果果皮果蝇的延长效果的影响。我们发现，蔓越莓可以延长富含糖和蛋白质含量适中的饮食的苍蝇的寿命，并在富含高糖蛋白饮食的苍蝇中更突出地增加寿命，但不会延长或缩短苍蝇的寿命。我们进一步证明，补充蔓越莓诱导的寿命延长与终身生殖产量增加和应力反应基因的更高表达有关。我们还表明，蔓越莓可以改善喂养高脂饮食的蝇的生存。这项研究揭示了饮食中大营养素在蔓越莓补充的促进作用中的关键作用，并指出了考虑饮食组成在实施促进健康衰老的干预措施中的重要性。这项工作已被接受在老年生物科学杂志上发表（2013年）。未来的工作将被更多地指导，以了解蔓越莓补充效应的分子机制及其在调节寿命中的饮食大量营养素之间的相互作用。这将为促进健康衰老的干预措施提供全面的看法，并有助于改善干预措施。 衰老研究中的一个重要问题是评估HealthSpan，因为衰老研究的基本目标不仅是增加寿命，而且可以通过保留功能显着改善健康范围。衰老与许多行为变化有关，例如运动活动的逐渐下降，这是健康范围的参数。许多工具可用于测量模型生物和人类的运动活动。但是，与年龄相关的行为变化仍然很少理解，这主要是由于缺乏能够记录任何生物体高分辨率的终身行为变化的工具。我们以前已经开发了一种行为监控系统（BMS），该系统可以在墨西哥果蝇（Mexflies）一生中以精细的分辨率记录六种类型的行为。 Mexflies已广泛用于人口和衰老干预研究。与Drs合作。墨西哥的Pablo Liedo，加州大学戴维斯分校的Joanne Chiu和James Carey和Pennington的Donald Ingram，我们利用BMS的优势研究了使用高分辨率的Mexflies中的高分辨率LIFELONG RECORTING DATA，调查了饮食对运动相关的运动量，睡眠数量和质量的影响。我们发现，在营养平衡饮食下的果蝇的活动特征几乎没有与年龄相关的变化，而次优饮食的苍蝇的幅度幅度显着降低，而老年人的睡眠质量则降低。这项工作已发表在《科学报告》（2013年）中。未来的工作将是利用BMS评估任何由任何延长的干预措施引起的终身行为变化，以阐明衰老干预措施对HealthSpan的影响。我们还将为果蝇开发类似的BMS，以研究终身行为变化的分子机制。 总而言之，我们已经确定了饮食中的大量营养素对果蝇中含蔓越莓营养的延长效果的影响。我们已经通过分析不同饮食条件下MEXFLIS的终生行为变化来评估饮食对HealthSpan的影响。这些发现为我们未来的研究奠定了基础，该研究致力于了解饮食中的大量营养素与营养剂或药品之间相互作用的分子机制。 这些研究应提供有价值的信息，以开发有效的干预措施来促进人类健康衰老。该项目应促进转化老年度分支机构的目标和美国国家老龄化研究所的整体任务。