Oxidative stress and the pathogenesis of sarcopenia and disability in older women

氧化应激以及老年女性肌肉减少症和残疾的发病机制

基本信息

批准号：
8717543
负责人：
RICHARD D SEMBA
金额：
$ 23.25万
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 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8717543
关键词：
Activities of Daily Living Address Adult Advanced Glycosylation End Products Aging Animal Disease Models Animal Model Area Atherosclerosis Atrophic condition of skin Binding Biology Body Composition Cardiovascular Diseases Cessation of life Cohort Studies Communities Development Disease Elderly Enrollment Enzyme-Linked Immunosorbent Assay Expenditure Gene Delivery Genes Goals Grant Greek Health Healthcare Hormones Hospitalization Human Impaired cognition Integral Membrane Protein Intervention Investigation Italy Knowledge Life Longevity Measures Membrane Mus Mutant Strains Mice Mythology Names Outcome Oxidative Stress Participant Pathogenesis Pathway interactions Performance Phenotype Plasma Play Process Prospective Studies Public Health Renal Hypertension Risk Role Serum Skeletal Muscle Speed Therapeutic Transgenic Mice Walking Wild Type Mouse Woman aging gene anti aging arterial stiffness base disability falls follow-up grasp high risk human disease in vivo insight interest men mortality muscle form muscle strength new therapeutic target novel older women overexpression population based prevent 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 for interventions that reduce the ris of sarcopenia and disability. In the first two cycles 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 also showed that advanced glycation end products (AGEs) and receptor for AGEs (RAGE) were independently associated with poor muscle strength, disability, and mortality. In the third cycle, we propose to examine the relationship between the "anti-aging" hormone klotho and sarcopenia in older adults. Klotho is a recently discovered hormone that plays a role in suppressing oxidative stress and is implicated in the pathogenesis of sarcopenia. We hypothesize that adults with low serum klotho levels have (1) lower skeletal muscle mass and strength and slower walking speed, and (2) greater decline of skeletal muscle mass and strength and walking speed, and (3) higher risk of mobility limitation, disability, and death. To address these hypotheses, we will study the relationship between serum klotho concentrations and the above outcomes in 2734 adults in the Health, Aging, and Body Composition (Health ABC) Study, a community-based prospective study of aging. We will measure serum klotho at baseline and examine the relationship between serum klotho and skeletal muscle mass, muscle strength, walking speed, mobility limitation, disability, and mortality over follow-up. Our propose studies will expand the knowledge of klotho into a novel area of investigation that focuses on sarcopenia and aging in community-dwelling adults.