Oxidative Stress and the Pathogeneisis of Sarcopenia and Disability in Older Wome

氧化应激与老年女性肌肉减少症和残疾的发病机制

基本信息

批准号：
7908823
负责人：
RICHARD D SEMBA
金额：
$ 33.46万
依托单位：
JOHNS HOPKINS UNIVERSITY
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 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7908823
关键词：
Activities of Daily Living Address Adult Advanced Glycosylation End Products Aging Antioxidants Area Baltimore Binding Biology Blood Carotenoids Chronic Disease Cohort Studies Communities DNA Data Development Diet Diet Modification Distal Elderly Expenditure Food Funding Future Goals Grant Healthcare High temperature of physical object Hospitalization Inflammation Intake Intervention Intervention Trial Investigation Italy Knowledge Lipids Measures Muscle Muscle Weakness Nutrient Outcome Oxidative Stress Pathogenesis Pathway interactions Performance Play Prevention Principal Investigator Process Proteins Public Health Research Risk Risk Factors Role Selenium Serum Skeletal Muscle Speed Time Translational Research Walking Women&apos s Health base cohort cooking density disability falls fruits and vegetables innovation insight modifiable risk mortality muscle form muscle strength novel older women oxidative damage population based prevent programs prospective public health relevance receptor receptor for advanced glycation endproducts sarcopenia

项目摘要

DESCRIPTION (provided by applicant): Disability threatens the independence of many older adults and results in substantial late-life health care needs and associated expenditures. Sarcopenia, defined as loss of muscle mass and strength, plays a central role in disability. Our long-term goals are to gain insight into the processes that underlie the development of sarcopenia and disability and to identify possible strategies that reduce the risk of sarcopenia and disability. In the first cycle of this R01, we examined the hypothesis that oxidative stress contributes to loss of muscle strength, decline in physical performance, disability, and mortality in older adults, and our findings support this paradigm. We now build upon the previous findings with important new preliminary data that implicate advanced glycation end products (AGEs) with poor muscle strength and mortality. AGEs are bioactive molecules that have recently been identified in the pathogenesis of multiple chronic diseases. AGEs occur in foods that have been cooked at very high temperatures, and ingested AGEs upregulate oxidative stress and inflammation through receptor for AGE (RAGE). RAGE also circulates in the blood and may serve as a decoy to bind free AGEs and prevent AGE-RAGE binding and activation of inflammation. Based upon knowledge of the AGE-RAGE pathway and our preliminary data, we hypothesize that older adults with elevated AGEs and circulating RAGE have an increased risk of sarcopenia, impaired physical performance, disability, and mortality. We propose to characterize the relationship between AGEs and circulating RAGE with these outcomes in adults from two different NIH-supported prospective, population-based cohort studies of aging, the Women's Health and Aging Study in Baltimore, and the InCHIANTI study in Italy. Our proposed studies will expand the knowledge of AGEs and their circulating receptors into a novel area of investigation that focuses on sarcopenia and aging in community-dwelling adults. If elevated serum AGEs are predictive of poor muscle strength, disability, and mortality, it would identify AGEs as a possible target for the prevention of disability in older adults. AGEs are a potentially modifiable risk factor, as circulating AGEs can be lowered by dietary modification and by pharmacological intervention. PUBLIC HEALTH RELEVANCE: This project is relevant to public health as it aims to characterize the relationship between advanced glycation end products, bioactive compounds found in high amounts in the western diet, and muscle weakness, disability, and mortality in older adults.

描述（由申请人提供）：残疾威胁到许多老年人的独立性，并导致大量的晚年医疗保健需求和相关支出。肌肉减少症被定义为肌肉质量和力量的丧失，在残疾中起着核心作用。我们的长期目标是深入了解肌肉减少症和残疾的发展过程，并确定降低肌肉减少症和残疾风险的可能策略。在本 R01 的第一个周期中，我们研究了氧化应激导致老年人肌肉力量丧失、身体机能下降、残疾和死亡率的假设，我们的研究结果支持了这一范式。现在，我们以之前的发现为基础，提供了重要的新初步数据，这些数据表明晚期糖基化终产物（AGE）与较差的肌肉力量和死亡率有关。 AGE 是最近在多种慢性疾病的发病机制中被发现的生物活性分子。 AGE 存在于高温烹调的食物中，摄入的 AGE 通过 AGE 受体 (RAGE) 上调氧化应激和炎症。 RAGE 也在血液中循环，可以作为结合游离 AGE 的诱饵，防止 AGE-RAGE 结合和炎症激活。根据对 AGE-RAGE 通路的了解和我们的初步数据，我们假设 AGE 和循环 RAGE 升高的老年人患肌肉减少症、身体机能受损、残疾和死亡的风险增加。我们建议通过 NIH 支持的两项不同的前瞻性、基于人群的老龄化队列研究（巴尔的摩的妇女健康和老龄化研究以及意大利的 InCHIANTI 研究）中的成人结果来描述 AGE 与循环 RAGE 之间的关系。我们提出的研究将把 AGE 及其循环受体的知识扩展到一个新的研究领域，重点关注社区成年人的肌少症和衰老。如果血清 AGE 升高预示着肌肉力量较差、残疾和死亡率，那么 AGE 就可以作为预防老年人残疾的可能目标。 AGE 是一个潜在的可改变的危险因素，因为循环 AGE 可以通过饮食调整和药物干预来降低。公共健康相关性：该项目与公共健康相关，因为它旨在描述晚期糖基化终产物、西方饮食中大量存在的生物活性化合物与老年人肌肉无力、残疾和死亡率之间的关系。