Dietary Restriction and Aging in Rhesus Monkeys

恒河猴的饮食限制和衰老

• 批准号: 8512638
• 负责人: RICKI J COLMAN
• 金额: $ 50.06万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512638
• 关键词: Adult; Age; Aging; Aging-Related Process; Animals; Behavioral; Biological Aging; Biology; Caloric Restriction; Calories; Chronic; Climate; Clinical; Data; Diabetes Mellitus; Dietary Intervention; Disease; Eating; Epidemic; Female; Funding; Future; Goals; Health; Intervention; Investigation; Laboratories; Learning; Life; Longevity; Longitudinal Studies; Macaca mulatta; Malnutrition; Mammals; Medical; Metabolic; Metabolism; Modeling; Monitor; Monkeys; Morbidity - disease rate; National Institute on Aging; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Pattern; Pharmaceutical Preparations; Physiology; Piper; Primates; Program Research Project Grants; Public Health; Publications; Relative (related person); Research; Rodent; Rodent Model; Science; Span 40; System; Testing; Time; Work; age related; aging population; base; cerebral atrophy; cost; dietary restriction; environmental intervention; feeding; improved; insight; interest; male; mortality; prevent; programs; response; sarcopenia

DESCRIPTION (provided by applicant): In 1989, we began a study to determine whether or not adult-onset DR could slow the aging process in a primate species. This work was originally supported by an R01, and since 1994 has been funded by the National Institute on Aging (NIA) through the Program Project Grant (P01) mechanism. In January 2010 we submitted an application to NIA for continued funding of this project through the P01 mechanism that reviewed very well (18th percentile). Unfortunately, due to the current funding climate, it is unlikely that this application will be funded. We were therefore strongly encouraged by our NIA program officer to submit this R01 to continue the key aspects of this long-term study. Accordingly, we request support to span 2011 - 2016 (when the study would be in its 27th year) to continue this unique and exciting endeavor to its natural conclusion of maximum lifespan. Through our previous 20+ years of research we have demonstrated the suitability of the rhesus monkey aging model and, quite recently, the efficacy of DR in slowing major features of biological aging. These include sarcopenia as well as delaying morbidity, brain atrophy and mortality. Importantly, these latter studies are not yet complete as 30 of the original 76 monkeys (39%) are alive. Thus, the goal of this application is to get five years closer to having data for all animals on healthspan and lifespan. There are two Specific Aims: Specific Aim 1: To determine DR's influence on the rate of aging in a primate species by evaluating indicators of biological age, healthspan and disease patterns. We are testing a moderate adult-onset DR (30% calorie reduction) on female and male rhesus monkeys and have made significant progress on this Aim; however, fully achieving it will require several more years as the study's oldest monkeys (~30 years) are only now becoming quite old (average rhesus lifespan is ~27 years, maximum lifespan is ~40 years). Over the next 5 years, these animals will be of an age at which increases of age-related morbidity are expressed. Specific Aim 2: To determine DR's influence on maximal lifespan in a primate species. While we have made significant progress in determining DR's influence on the rate of aging we are not yet able to determine the ability of DR to alter maximal lifespan in a primate species. Over the next 5 years, the animals will be rapidly approaching an age at which will be able to determine whether DR increases maximal lifespan. Gerontologists have eagerly awaited these data for decades. Based on the media response to our recent Science publication our study is of broad general interest. A major clinical implication is that DR represents a metabolic state opposite that of type 2 diabetes which, to date, has been completely prevented by DR in our monkeys. This observation has obvious public health implications while an obesity/diabetes epidemic is prominent. These data may have a very significant public health impact by demonstrating the health and longevity benefits triggered by DR in primates and should stimulate efforts to mimic these effects by drug or dietary interventions.

描述（由申请人提供）：1989 年，我们开始了一项研究，以确定成年发病的 DR 是否可以减缓灵长类动物的衰老过程。这项工作最初得到 R01 的支持，自 1994 年以来一直由国家老龄化研究所 (NIA) 通过计划项目拨款 (P01) 机制提供资助。 2010 年 1 月，我们向 NIA 提交了一份申请，要求通过 P01 机制继续资助该项目，审查结果非常好（第 18 个百分点）。不幸的是，由于当前的融资环境，该申请不太可能获得资助。因此，我们的 NIA 项目官员强烈鼓励我们提交这份 R01，以继续这项长期研究的关键方面。因此，我们请求在 2011 年至 2016 年期间提供支持（届时该研究将进入第 27 个年头），以继续这一独特且令人兴奋的努力，以自然结束最长寿命。通过我们过去 20 多年的研究，我们已经证明了恒河猴衰老模型的适用性，并且最近还证明了 DR 在减缓生物衰老的主要特征方面的功效。这些包括肌肉减少症以及延迟发病、脑萎缩和死亡率。重要的是，后面的这些研究尚未完成，因为最初的 76 只猴子中有 30 只 (39%) 还活着。因此，该应用程序的目标是在五年内获得所有动物的健康寿命和寿命数据。具体目标有两个： 具体目标 1：通过评估生物年龄、健康寿命和疾病模式指标来确定 DR 对灵长类物种衰老速度的影响。我们正在雌性和雄性恒河猴身上测试中度成年发病 DR（热量减少 30%），并在这一目标上取得了重大进展；然而，完全实现这一目标还需要几年的时间，因为该研究中最年长的猴子（约 30 岁）现在才变得相当老（恒河猴的平均寿命约为 27 年，最长寿命约为 40 年）。在接下来的5年里，这些动物将达到与年龄相关的发病率增加的年龄。具体目标 2：确定 DR 对灵长类动物最大寿命的影响。虽然我们在确定 DR 对衰老速度的影响方面取得了重大进展，但我们还无法确定 DR 改变灵长类动物最大寿命的能力。在接下来的 5 年里，动物将迅速接近能够确定 DR 是否可以延长最大寿命的年龄。几十年来，老年学家一直热切地等待着这些数据。根据媒体对我们最近发表的《科学》杂志的反应，我们的研究引起了广泛的普遍兴趣。一个主要的临床意义是，DR 代表了一种与 2 型糖尿病相反的代谢状态，迄今为止，我们的猴子中的 DR 已完全预防了这种代谢状态。在肥胖/糖尿病流行十分突出的情况下，这一观察结果具有明显的公共卫生意义。这些数据可能会通过证明 DR 对灵长类动物带来的健康和长寿益处而产生非常重大的公共健康影响，并且应该刺激通过药物或饮食干预来模拟这些效果的努力。