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The role of the gut microbiota in sarcopenia

肠道微生物群在肌肉减少症中的作用

基本信息

批准号：
10193399
负责人：
JOHN Joseph MCCARTHY
金额：
$ 22.24万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10193399
关键词：
Adult Age Age-Months Aging Amino Acids Autophagocytosis Biological Assay Cell Count Cell physiology Defect Development Elderly Endocrine Etiology Exercise Exhibits Fiber Fibrosis Future Grant Impairment Inflammation Injury Interleukin-6 Intestinal permeability Intestines Investigation Knock-out Life Expectancy Maintenance Measures Metabolic Motor Mus Muscle Muscle function Oxidative Stress Performance Persons Phenotype Polyethylene Glycols Population Predisposition Quality of life Research Resistance Risk Factors Role Serum Signal Transduction Skeletal Muscle TLR4 gene TNF gene Testing Woman aged dysbiosis experimental study falls fecal microbiota fluorescein isothiocyanate dextran frailty functional independence functional loss gut bacteria gut dysbiosis gut microbiome gut microbiota improved men mitochondrial DNA mutation muscle aging muscle form muscle strength nerve supply novel prevent regeneration following injury response sarcopenia satellite cell sedentary skeletal muscle wasting systemic inflammatory response therapeutic target

项目摘要

Summary A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and function. Recent estimates indicate that up to one-third of the elderly population may suffer from frailty. Frailty often leads to loss of functional independence and is among the leading risk factors for falls in the elderly. In fact, as life expectancy continues to increase, the maintenance of muscle strength is an important factor that contributes to a higher quality of life. Although the etiology of sarcopenia remains to be determined, proposed contributing factors include the loss of innervation and motor unit decline, oxidative stress, aberrant autophagy and inflammation. There is emerging evidence for the existence of a gut-skeletal muscle axis. On the basis of this connection, there has been much speculation that dysbiosis of the gut microbiota might have a role in the development of sarcopenia. While plausible mechanisms have been proposed through which dysbiosis might contribute to the development of sarcopenia, there remains a paucity of direct evidence to support such mechanisms. The purpose of this exploratory grant is to test the hypothesis that dysbiosis of the gut microbiota promotes sarcopenia by inducing a state of anabolic resistance in skeletal muscle through TLR4 hyperactivation of mTORC1 signaling. To test this hypothesis, the following aims will be pursued: Aim 1: Determine if the gut microbiota from aged mice can induce sarcopenia in adult mice; Aim 2: Determine if the gut microbiota from adult mice can rescue sarcopenia in old mice. If the results of the proposed experiments provide evidence to support the hypothesis, a future R01 application will seek to rigorously test the proposed mechanism by determining if a skeletal muscle-specific TLR4 knockout prevents sarcopenia despite low-grade systemic inflammation induced by gut microbiota dysbiosis.

总结