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，以确定成人发作的DR是否可以减慢灵长类动物的衰老过程。这项工作最初得到了R01的支持，自1994年以来，由美国国家老化研究所（NIA）通过计划项目赠款（P01）机制资助。 2010年1月，我们通过P01机制向NIA提交了一份申请，以继续为该项目提供资金，该机制非常好（第18个百分点）。不幸的是，由于当前的资金氛围，此应用程序不太可能资助。因此，我们的NIA计划官员强烈鼓励我们提交此R01，以继续这项长期研究的关键方面。因此，我们要求对2011年跨度至2016年的支持（当时该研究成立27年）继续这一独特而令人兴奋的努力，以实现其最大寿命的自然结论。在过去的20多年的研究中，我们证明了恒河猴老化模型的适用性，并且最近，DR在减慢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率，脑萎缩和死亡率。重要的是，这些后一种研究尚未完成，因为原始76只猴子中有30个还活着。因此，该应用程序的目的是使五年更接近HealthSpan和LifeSpan上所有动物的数据。有两个具体的目的：特定目的1：通过评估生物年龄，健康状态和疾病模式的指标来确定DR对灵长类动物衰老的影响。我们正在测试女性和雄性恒河猴的中度成年人发作的DR（降低30％卡路里），并在这一目标上取得了重大进展。但是，由于研究的最古老的猴子（约30年）才变得很老（恒河所的平均寿命约为27年，最大寿命约为40年），因此完全需要几年的时间才能完全实现。在接下来的5年中，这些动物将是表达与年龄相关的发病率增加的年龄。特定目的2：确定DR对灵长类动物中最大寿命的影响。尽管我们在确定DR对衰老率的影响方面取得了重大进展，但我们尚无法确定DR改变灵长类动物中最大寿命的能力。在接下来的5年中，这些动物将迅速接近一个年龄，在这种年龄中，将能够确定DR是否会增加最大寿命。数十年来，老年医师一直热切期待这些数据。根据媒体对我们最近的科学出版物的反应，我们的研究具有广泛的一般兴趣。一个主要的临床意义是，DR代表了与2型糖尿病相反的代谢状态，迄今为止，DR已被DR在我们的猴子中完全阻止。这种观察具有明显的公共卫生影响，而肥胖/糖尿病的流行很突出。这些数据可能通过证明DR在灵长类动物中触发的健康和寿命益处而产生非常重大的公共卫生影响，并应刺激通过药物或饮食干预措施模仿这些影响的努力。