Dietary Supplements and Inflammation Phase-2 (Metabolic Mechanisms and Interventions for Healthy Aging in Females)

项目摘要/摘要：老年女性比男性更有可能患有损害健康的疾病或残疾 独立生活的活动，并威胁生活质量。广泛损害健康和健康的机制 人们对老年女性的幸福感并不完全了解，但中年过渡到更年期，以及 随之而来的是循环中雌激素的减少，这是女性寿命中一个特别显著的里程碑。数不胜数 研究记录了更年期卵巢激素的丢失和卵巢激素的丢失之间的联系 在认知、体能和免疫健康领域的保护作用。雌激素通常作用于这些 线粒体氧化磷酸化支持的优化细胞代谢的系统。雌激素丢失 中年与氧化应激增加和炎症反应增强有关。荷尔蒙 替代疗法是用来缓解更年期症状和体征的，但它的广泛作用是 不受欢迎的风险，有时甚至危及生命。确定互补的战略，以恢复适当的 围绝经期和绝经后妇女代谢和免疫活动的平衡可能减慢与年龄相关的速度 认知、身体和免疫健康下降，而不会招致其他与年龄相关的疾病的风险。这个 生酮饮食可能会满足这些标准，因为食用这种高脂肪/低碳水化合物的饮食会从根本上改变 代谢特征，改变对葡萄糖的依赖，有利于脂肪衍生的酮体，同时也 消炎消炎。与这一观点一致的是，我们的初步数据表明，生酮饮食 改善老年雌性大鼠的认知和线粒体功能。这个项目的目标是阐明 生酮饮食减缓与年龄相关的多个功能区衰退的机制 女性寿命。该项目将使用正常衰老的大鼠来1)确定生酮饮食对 与年龄相关的脑、肌肉和免疫功能下降；2)决定生酮饮食的保护作用 手术雌激素缺乏的中年女性的认知、身体功能和免疫状况。这些 在控制良好的衰老和更年期动物模型中研究营养性酮症将具有重要意义，因为 它们可以提供必要的机械性见解来指导适当的翻译和开发 医生可以向老年妇女推荐的主要或辅助治疗的饮食干预措施 过渡到更年期，并面临与年龄相关的疾病的风险。更广泛地说，识别特定性别和 适合年龄的饮食指南，以减缓驱动生理和细胞的基本机制 老龄化将在很大程度上改善老年妇女的健康状况，减少对激素替代的依赖 将治疗作为对抗更年期症状的一线治疗。这些目标是在科学的 南卡罗来纳大学关于膳食补充剂的科布雷范围，并将完成严格的 关于衰老导致罹患高血压风险增加的潜在分子和细胞机制的科学研究 绝经前和绝经后妇女的疾病(阿尔茨海默病、骨质疏松症)。

Project Summary/Abstract: Older women are more likely than men to live with disease or disability that impairs activities for independent living and threatens quality of life. The mechanisms that broadly diminish health and well-being among aging women are not fully understood, but the transition into menopause at mid-life, and the ensuing decrease in circulating estrogens, is a particularly salient milestone in the female lifespan. Numerous studies document an association between the loss of ovarian hormones at menopause and the loss of their protective effects in domains of cognition, physical ability, and immune health. Estrogens typically act upon these systems to optimize cellular metabolism supported by mitochondrial oxidative phosphorylation. Loss of estrogens at middle-age is associated with increased oxidative stress and enhanced inflammatory responses. Hormone replacement therapy is prescribed to relieve signs and symptoms of menopause, but its broad actions carry undesirable and sometimes life-threatening risks. Identifying complementary strategies that restore the proper balance of metabolic and immune activities in peri- and post-menopausal women could decelerate age-related declines in cognitive, physical, and immune health without incurring risk for other age-associated diseases. The ketogenic diet may fulfill these criteria as consuming this high fat/low carbohydrate diet fundamentally alters metabolic profiles, shifting dependence away from glucose in favor of fat-derived ketone bodies, while also attenuating inflammation. Consistent with this view our preliminary data demonstrate that a ketogenic diet improved cognitive and mitochondrial function in aging female rats. The goal of this project is to elucidate the mechanisms by which the ketogenic diet decelerates age-related decline in multiple functional domains over the female lifespan. This project will use normally aging rats to 1) determine sex-specific effects of ketogenic diet on age-related decline of brain, muscle, and immune function and 2) determine protective effects of ketogenic diet on cognition, physical function, and immune profiles in surgically estrogen-deficient, middle-aged females. These studies of nutritional ketosis in well-controlled animal models of aging and menopause will be significant because they can provide the necessary mechanistic insights to guide the translation and development of appropriate dietary interventions that physicians can recommend as primary or adjuvant therapies to older women transitioning into menopause and at risk for age-related disorders. More broadly, identifying sex-specific and age-appropriate dietary guidelines to decelerate fundamental mechanisms that drive physiological and cellular aging will broadly improve health outcomes for older women and reduce reliance on hormone replacement therapy as a first-line treatment to combat symptoms of menopause. These objectives are within the scientific scope of the University of South Carolina’s COBRE on Dietary Supplements and will accomplish rigorous scientific research on the underlying molecular and cellular mechanisms of aging leading to increased risk of disease (Alzheimer's disease, sarcopenia) in pre- and post-menopausal women.