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

• 批准号: 7649677
• 负责人: RICHARD D SEMBA
• 金额: $ 32.97万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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/7649677
• 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' 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

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）：残疾威胁着许多老年人的独立性，并导致大量的晚期医疗保健需求和相关支出。被定义为肌肉质量和力量丧失的肌肉减少症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发展的过程，并确定降低肌肉减少症和残疾风险的可能策略。在此R01的第一个周期中，我们研究了以下假设：氧化应激有助于肌肉力量的丧失，身体表现的下降，残疾和老年人死亡率，我们的发现支持了这一范式。现在，我们基于先前的发现，具有重要的新初步数据，这些数据暗示了肌肉力量和死亡率差的高级糖基化终产物（年龄）。年龄是最近在多种慢性疾病的发病机理中鉴定出的生物活性分子。年龄发生在非常高温下烹饪的食物中，并且摄取的年龄会通过年龄（愤怒）上调通过受体的氧化应激和炎症。愤怒还会在血液中循环，可以用作诱饵以结合自由年龄并防止年龄的结合和激活炎症。基于对年龄段途径和我们的初步数据的了解，我们假设年龄升高和循环愤怒的老年人患有肌肉减少症的风险增加，身体表现受损，残疾和死亡率受损。我们建议在两种不同的NIH支持的前瞻性，基于人群的衰老研究，巴尔的摩的妇女健康和衰老研究以及意大利的Inchianti研究的成年人中表征年龄与循环愤怒之间的关系。我们提出的研究将将年龄及其循环受体的知识扩展到一个新的调查领域，该领域侧重于肌肉减少症和社区成年人的衰老。如果血清年龄升高可以预测肌肉力量不佳，残疾和死亡率，则将确定年龄是预防老年人残疾的可能目标。年龄是一个潜在的可修改风险因素，因为循环年龄可以通过饮食改造和药理干预来降低。公共卫生相关性：该项目与公共卫生有关，旨在表征西方饮食中高级糖化最终产品，生物活性化合物之间的关系，以及老年人的肌肉无力，残疾和死亡率。