Caloric Restriction and Aging in Eyes

热量限制和眼睛老化

基本信息

批准号：
7640503
负责人：
PETER GOURAS
金额：
$ 31.63万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7640503
关键词：
4 hydroxynonenal Address Advanced Glycosylation End Products Age Age related macular degeneration Aging Amyloid Animals Apolipoprotein E Atrophic Be++ element Beryllium Biological Caloric Restriction Cataract Clinical Data Development Diet Disease Elderly Electron Microscopy Enzymes Eye Fishes Glaucoma Goals Health Heat shock proteins Histology Histopathology Human Immunohistochemistry Incidence Institutes Intervention Life Light Longevity Macaca mulatta Macular degeneration Matched Group Measurement Measures Modeling Molecular Chaperones Monitor Monkeys Older Population Optic Nerve Oregon Organ Oxidative Stress Population Primates Proteins Rattus Recording of previous events Reporting Research Research Personnel Resources Retina Rodent Saimiri Skeletal Muscle Specimen Stress Structure of sinus venosus of sclera TIMP3 gene Testing Tissues Vitronectin age effect age related aged fly insight lens man non-invasive monitor nonhuman primate oxidative damage prevent programs receptor for advanced glycation endproducts research clinical testing research study

项目摘要

DESCRIPTION (provided by applicant): Dietary caloric restriction (CR) is the only intervention demonstrated through extensive experimentation to extend the lifespan of a variety of animals with short lifespans. Whether CR can also extend the life of humans remains unanswered. The National Institutes of Aging Caloric Restriction Study maintains long-term colonies of nonhuman primates which provide the best available model to address this question. As part of this unique resource, rhesus and squirrel monkeys, including age-matched groups maintained long term (15+ years) on 30% caloric restricted or ad libitum (AL) diets, are evaluated for many health parameters and markers of aging. However, there has been no in-depth study of ocular aging in these monkeys. Because of its accessibility to non-invasive monitoring, the eye is an ideal organ to evaluate longitudinally whether CR can retard the occurrence of aging and age-related disease. Observations in rats suggest that CR delays age-related changes in the lens and retina by reducing oxidative stress. Since some of the beneficial effects of CR reported in aging rodents have also been observed in aging monkeys such as reduced oxidative stress in skeletal muscle, we hypothesize that CR will reduce oxidative stress and delay aging and age-related disease in the eye. There are two major goals to our project: 1) To determine by comprehensive clinical examinations whether CR retards the development of aging and age related ocular disease (macular degeneration, cataract, glaucoma, optic nerve atrophy) in these monkeys. 2) To confirm and support the clinical observations by histological studies of the ocular tissue using markers of age-related degeneration and oxidative stress, comparing tissues from CR with those from AL monkeys. This research can provide new insights into the cause and possible treatment of human age-related ocular disorders. Because many of these primates are near the end of their lifespan, there is an element of urgency in our goal to correlate noninvasive clinical testing prior with post mortem histology.

描述（由申请人提供）：饮食热量限制（CR）是通过广泛的实验证明的唯一干预措施，以延长寿命短的各种动物的寿命。 CR是否也可以延长人类的寿命仍未得到解答。美国国家老龄化热量限制研究的研究所维持非人类灵长类动物的长期殖民地，为解决这个问题提供了最佳的可用模型。作为这一独特资源的一部分，评估了许多健康参数和衰老的标志物，其中评估了评估了30％卡路里的限制或自由（AL）饮食的长期（15岁以上）的年龄匹配的猴子，包括长期（15岁以上）的群体。但是，在这些猴子中没有对眼部衰老的深入研究。由于其对非侵入性监测的可及性，眼睛是纵向评估CR是否可以阻止衰老和与年龄有关的疾病的理想器官。大鼠的观察结果表明，CR延迟通过减少氧化应激而与年龄相关的镜头和视网膜变化。由于在衰老的猴子中也观察到了CR在衰老啮齿动物中报道的某些有益作用，例如骨骼肌氧化应激减少，因此我们假设CR会减少眼睛中氧化应激，延迟衰老和与年龄相关的疾病。我们的项目有两个主要目标：1）通过全面的临床检查来确定CR是否会延迟这些猴子中衰老和与年龄相关的眼部疾病的发展（黄斑变性，白内障，青光眼，视神经萎缩）。 2）使用与年龄相关的变性和氧化应激的标记来确认和支持眼组织的临床观察，将CR的组织与Al猴子的组织进行比较。这项研究可以为与人类年龄相关的眼部疾病的原因和可能治疗提供新的见解。由于这些灵长类动物中的许多人都接近其寿命的尽头，因此我们的目标是将非侵入性临床测试与死后组织学相关联。