DIETARY RESTRICTION AND AGING

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 目的：探讨饮食限制延缓衰老过程的可能性 在一个 非人类灵长类物种。该计划项目提供了丰富的新内容 有关衰老生物学以及饮食控制如何影响的信息 变老的过程。 进展： 猴子吃的热量比全营养饮食少 30% 健康状况优于研究对照组。减少热量摄入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，正如在 啮齿动物。在饮食受到限制的猴子中，糖尿病的发生率较低。动物 允许自由饮食的人患糖尿病或糖尿病前期疾病的几率更高。 限制性饮食的猴子的空腹基础胰岛素和葡萄糖浓度较低 饮食。限制饮食的猴子的脂肪质量和去脂质量均较低。 低热量饮食的猴子患脊柱关节炎的迹象较少 随着年龄的增长，这一点在恒河猴和人类身上都会显现出来。卡路里更少 可以降低患血管疾病的风险。热量限制改变了循环中的低密度脂蛋白 可能抑制动脉粥样硬化形成的方式。热量限制会延缓一些年龄 骨骼肌的依赖性生理和生化变化，包括 氧化损伤。控制热量限制并没有扰乱月经周期 母猴。下一个时期的学习应该更加深入 研究中最年长的猴子现在已经真正老了。在这个阶段，与年龄相关的 疾病和病症出现得更频繁，包括成人发病的糖尿病， 骨质疏松症、癌症、肥胖、高血压和骨骼肌质量损失。 这项研究使用了动物服务、化验服务和病理学服务。 出版物： Anderson RM、Colman RJ：灵长类衰老研究的前景和观点。 抗氧化剂。氧化还原信号。 14(2):203-205, 2011。PMCID：PMC3000241，PMID：20712396。 Anderson RM、Weindruch R：代谢重编程、热量限制和衰老。 趋势内分泌。代谢物。 21(3):134-141, 2010。PMCID：PMC2831168，PMID： 20004110。 本德林 B、卡努 E、威莱特 AA、卡斯特曼 EK、迈凯轮 DG、科斯马特卡 KJ、徐 G、菲尔德 AS、 Colman RJ、Coe CL、Weindruch R、Alexander AL、Johnson SC：衰老和衰老的影响 恒河猴白质的热量限制。神经生物学老化。 2010 年 6 月 10 日。 [Epub 打印前] PMCID：PMC2939965，PMID：20541839 Colman RJ、Anderson R：非人类灵长类动物热量限制。抗氧化剂。氧化还原信号。 14(2):229-239, 2011。PMCID：PMC3000242。 PMID：20698791。 Fowler CG、Chiasson KB、Leslie TH、Thomas D、Beasley TM、Kemnitz JW、Weindruch R： 恒河猴的听觉功能：衰老和热量限制的影响 五年后，威斯康星州的猴子。听到。资源。 261（1-2）：75-81，2010。PMCID： PMC2855903，PMID：20079820。 卡斯特曼 EK、威莱特 AA、科 CL、本德林 BB、科斯马特卡 KJ、迈凯伦 DG、徐 G、卡努 E、Field AS、Alexander AL、Voytko ML、Beasley TM、Colman RJ、Weindruch R、Johnson SC：热量限制饮食可减少脑铁积累并保持运动能力 老恒河猴的表现。神经科学杂志。 30(23):7940-7947, 2010。PMCID： PMC2898557，PMID：20534842。 McKiernan SH、Colman RJ、Lopez M、Beasley TM、Aiken JM、Anderson RM、Weindruch R： 热量限制延迟了恒河猴衰老诱导的细胞表型 骨骼肌。过期。杰龙托尔。 46(1):23-29, 2011。PMCID：PMC2998549，PMID： 20883771 威莱特 AA、本德林 BB、迈凯轮 DG、卡努 E、卡斯特曼 EK、科斯马特卡 KJ、徐 G、菲尔德 AS、Alexander AL、Colman RJ、Weindruch RH、Coe CL、Johnson JC：与年龄相关 与白细胞介素 6 相关的神经体积和微观结构的变化 老恒河猴的热量限制饮食可以改善这种情况。神经影像。 51(3):987-994，2010。PMID：20298794，PMCID：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、 Field AS、Alexander AL、Colman RJ、Voytko ML、Weindruch RH、Coe CL、Johnson SC： 同型半胱氨酸、神经萎缩和热量限制对恒河猴的影响。 神经生物学老化。 2010 年 8 月 4 日。[印刷前的电子版]。 PMID：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.