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

膳食补充剂和炎症第二阶段（女性健康老龄化的代谢机制和干预措施）

• 批准号: 10395220
• 负责人: Joseph Aloysius McQuail
• 金额: $ 13.79万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395220
• 关键词: Adjuvant Therapy; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Animal Model; Animals; Attenuated; Automobile Driving; Blood Circulation; Brain; Carbohydrates; Cell Aging; Cell physiology; Cells; Centers of Research Excellence; Cerebrum; Cognition; Cognitive; Consumption; Data; Degenerative Disorder; Dependence; Development; Diet; Dietary Intervention; Disease; Energy Metabolism; Equilibrium; Estrogen Therapy; Estrogens; Estrus; Extravasation; Fatty acid glycerol esters; Female; Glucose; Goals; Health; Hormone replacement therapy; Hormones; Immune; Immunity; Immunologics; Impairment; In Vitro; Independent Living; Inflammation; Inflammatory; Inflammatory Response; Intervention; Intestinal permeability; Ketone Bodies; Ketosis; Knowledge; Lead; Life; Life Style; Link; Longevity; Malignant Neoplasms; Measures; Medium chain triglycerides; Menopausal Symptom; Menopause; Metabolic; Metabolism; Mitochondria; Molecular; Mucosal Immune Responses; Muscle; Muscle function; Nutritional; Nutritional Study; Operative Surgical Procedures; Outcome; Ovarian hormone; Oxidative Phosphorylation; Oxidative Stress; Perimenopause; Personal Satisfaction; Phase; Physical Function; Physicians; Physiological; Postmenopause; Pre-Clinical Model; Predisposition; Premenopause; Property; Quality of life; Randomized; Rattus; Recommendation; Regulation; Research; Research Project Grants; Risk; Signs and Symptoms; Skeletal Muscle; South Carolina; Stroke; Supplementation; System; Testing; Translations; Universities; Woman; Women' s Health; Work; age related; biological sex; body system; cognitive function; combat; dietary control; dietary guidelines; dietary supplements; disability; disorder risk; estrogenic; gut microbiota; healthy aging; hormone therapy; immune function; immune health; improved; in vivo; insight; ketogenic diet; ketogentic; lifestyle intervention; male; men; metabolic profile; microbiota; middle age; normal aging; older women; physical conditioning; prevent; protective effect; relating to nervous system; sarcopenia; sex; synaptic function; xenoestrogen

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.

项目摘要/摘要：老年女性比男性更容易患有疾病或残疾