DIETARY RESTRICTION AND AGING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目的：探讨饮食限制延缓衰老过程的可能性。 在一个 非人灵长类物种。该计划项目提供了丰富的新技术 关于衰老的生物学以及饮食控制如何影响的信息 变老的过程。 进度： 猴子在营养丰富的饮食中摄入的卡路里减少了30% 比研究对照组更健康。减少卡路里摄入量似乎可以延缓基本衰老 过程，并可能延长灵长类动物的最大寿命，如 啮齿动物。限制饮食的猴子患糖尿病的几率较低。动物 允许自由进食的人患糖尿病或糖尿病前期疾病的几率更高。 限制饮食的猴子空腹基础胰岛素和血糖浓度较低 节食。在限制饮食的猴子中，脂肪质量和脱脂质量都较低。 低卡路里饮食的猴子患脊椎关节炎的迹象较少，这是一种 这在恒河猴和人类身上都随着年龄的增长而表现出来。减少卡路里摄入 可能会降低患血管疾病的风险。卡路里限制改变了循环低密度脂蛋白 可以抑制动脉粥样硬化形成的方式。卡路里限制会延缓几个年龄- 骨骼肌中依赖的生理和生化变化，包括 氧化损伤。控制热量限制并没有扰乱月经周期 雌性猴子。下一阶段的学习应该更有洞察力，因为 研究中年龄最大的猴子现在真的很老了。在这一阶段，与年龄相关的 疾病和障碍出现的频率更高，包括成人发病的糖尿病， 骨质疏松症、癌症、肥胖症、高血压和骨骼肌群的丧失。 这项研究使用了动物服务、化验服务和病理服务。 出版物： 安德森·罗姆，科尔曼RJ：灵长类衰老研究的展望与展望。 反毒药。氧化还原信号。14(2)：203-205,2011。PMCID：PMC3000241，PMID：20712396。 Anderson RM，Weindruch R：代谢重新编程，卡路里限制与衰老。 趋势内分泌。梅塔布。21(3)：134-141,2010。PMCID：PMC2831168，PMID： 20004110。 Bendlin B，Canu E，Willette AA，Kastman EK，McLaren DG，Kosmatka KJ，Xu G，field as， 科尔曼·RJ，Coe CL，Weindruch R，Alexander AL，Johnson SC：衰老和 猕猴脑白质的卡路里限制。神经生物老化。2010年6月10日 [预印电子出版物]PMCID：PMC2939965，PMID：20541839 科尔曼RJ，安德森R：非人灵长类卡路里限制。反毒药。氧化还原信号。 14(2)：229-239,2011。PMCID：PMC3000242。20698791。 Fowler CG，Chiasson KB，Leslie Tth，Thomas D，Beasley TM，Kemnitz JW，Weindruch R： 恒河猴听功能：衰老和热量限制对听觉功能的影响 五年后，威斯康星州的猴子。听见。决议261(1-2)：75-81,2010年。PMCID： PMC2855903，PMID：20079820。 Kastman EK，Willette AA，Coe CL，Bendlin BB，Kosmatka KJ，McLaren DG，Xu G，Canu E，菲尔德AS，Alexander AL，Voytko ML，Beasley TM，Colman RJ，Weindruch R，Johnson SC：限制卡路里的饮食减少了大脑铁的积累，并保留了运动量 在老恒河猴身上的表现。J神经科。30(23)：7940-7947,2010。PMCID： PMC2898557，PMID：20534842。 McKiernan SH，Colman RJ，Lopez M，Beasley TM，Aiken JM，Anderson RM，Weindruch R： 热量限制延缓恒河猴衰老诱导的细胞表型 骨骼肌。实验杰隆托。46(1)：23-29,2011。PMCID：PMC2998549，PMID： 20883771 Willette AA，Bendlin BB，McLaren DG，Canu E，Kastman EK，Kosmatka KJ，Xu G，field AS，Alexander AL，Colman RJ，Weindruch RH，Coe CL，Johnson JC：年龄相关 与白介素6相关的神经体积和微结构的变化 改善了老年恒河猴的卡路里限制饮食。神经影像。 51(3)：987-994,2010年。PMID：20298794，PMC2877377。 威莱特AA，加拉格尔C，本德林BB，迈凯轮DG，卡斯特曼EK，卡努E，科斯马特卡KJ， 菲尔德AS，Alexander AL，Colman RJ，Voytko ML，Weindruch RH，Coe CL，Johnson SC： 同型半胱氨酸、神经萎缩和限制热量摄入对恒河猴的影响。 神经生物老化。2010年8月4日[印刷前的ePub]。20691506。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To explore the possibility that dietary restriction retards aging processes in a nonhuman primate species. This Program Project has provided a wealth of new information about the biology of aging and how the manipulation of diet can influence the process of growing old. PROGRESS: Monkeys eating 30 percent fewer calories of a nutritionally complete diet exhibit better health than study controls. Reduced caloric intake seems to slow basic aging processes and may extend the maximum life span in primates, as has been shown in rodents. Diabetes develops less frequently in monkeys on a restricted diet. Animals allowed to eat freely have a greater incidence of diabetic or pre-diabetic conditions. Fasting basal insulin and glucose concentrations are lower in monkeys on a restricted diet. Both fat mass and fat-free mass were lower in monkeys on a restricted diet. Monkeys on a reduced-calorie diet have fewer signs of spinal arthritis, a condition that manifests itself with age in both rhesus monkeys and humans. Fewer calories may reduce the risk of vascular disease. Caloric restriction altered circulating LDL in a manner that may inhibit atherogenesis. Caloric restriction retards several age- dependent physiological and biochemical changes in skeletal muscle, including oxidative damage. Controlled caloric restriction has not disrupted menstrual cycles of female monkeys. The next period of study should be even more insightful as the oldest monkeys in the study are now truly old. During this phase, age-related diseases and disorders appear more frequently, including adult-onset diabetes, osteoporosis, cancers, obesity, hypertension and the loss of skeletal muscle mass. This research used Animal Services, Assay Services and Pathology Services. PUBLICATIONS: Anderson RM, Colman RJ: Prospects and perspectives in primate aging research. Antiox. Redox Signal. 14(2):203-205, 2011. PMCID: PMC3000241, PMID: 20712396. Anderson RM, Weindruch R: Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol. Metab. 21(3):134-141, 2010. PMCID: PMC2831168, PMID: 20004110. Bendlin B, Canu E, Willette AA, Kastman EK, McLaren DG, Kosmatka KJ, Xu G, Field AS, Colman RJ, Coe CL, Weindruch R, Alexander AL, Johnson SC: Effects of aging and calorie restriction on white matter in rhesus macaques. Neurobiol Aging. 2010 Jun 10. [Epub ahead of print] PMCID: PMC2939965, PMID: 20541839 Colman RJ, Anderson R: Nonhuman primate calorie restriction. Antiox. Redox Signal. 14(2):229-239, 2011. PMCID: PMC3000242. PMID: 20698791. Fowler CG, Chiasson KB, Leslie TH, Thomas D, Beasley TM, Kemnitz JW, Weindruch R: Auditory function in rhesus monkeys: effects of aging and caloric restriction in the Wisconsin monkeys five years later. Hear. Res. 261(1-2):75-81, 2010. PMCID: PMC2855903, PMID:20079820. Kastman EK, Willette AA, Coe CL, Bendlin BB, Kosmatka KJ, McLaren DG, Xu G, Canu E, Field AS, Alexander AL, Voytko ML, Beasley TM, Colman RJ, Weindruch R, Johnson SC: A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys. J Neurosci. 30(23):7940-7947, 2010. PMCID: PMC2898557, PMID: 20534842. McKiernan SH, Colman RJ, Lopez M, Beasley TM, Aiken JM, Anderson RM, Weindruch R: Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle. Exp. Gerontol. 46(1):23-29, 2011. PMCID: PMC2998549, PMID: 20883771 Willette AA, Bendlin BB, McLaren DG, Canu E, Kastman EK, Kosmatka KJ, Xu G, Field AS, Alexander AL, Colman RJ, Weindruch RH, Coe CL, Johnson JC: Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys. Neuroimage. 51(3):987-994, 2010. PMID: 20298794, PMCID: PMC2877377. Willette AA, Gallagher C, Bendlin BB, McLaren DG, Kastman EK, Canu E, Kosmatka KJ, Field AS, Alexander AL, Colman RJ, Voytko ML, Weindruch RH, Coe CL, Johnson SC: Homocysteine, neural atrophy, and the effect of caloric restriction in rhesus monkeys. Neurobiol Aging. 2010 Aug 4. [Epub ahead of print]. PMID: 20691506.