The relationship between protein intake, gut microbiome, inflammaging and loss of mobility in older adults

老年人蛋白质摄入量、肠道微生物群、炎症和活动能力丧失之间的关系

• 批准号: 10370545
• 负责人: Samaneh Farsijani
• 金额: $ 12.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370545
• 关键词: 16S ribosomal RNA sequencing; Address; Adopted; Age; Aging; Biology; Biometry; Body Composition; Body Weight; Body mass index; C-reactive protein; Chronic; Clinical Research; Communities; Data; Diet; Dietary Proteins; Dietary intake; Elderly; Epidemiology; Food; Gait speed; Goals; Health; Health Policy; Immunoassay; Impairment; Individual; Inflammaging; Inflammation; Inflammatory; Interdisciplinary Study; Interleukin-6; Knowledge; Lead; Link; Long-Term Effects; Mass Spectrum Analysis; Measures; Mediating; Mediation; Mediator of activation protein; Muscle; Muscle Proteins; Muscle function; Nutritional Study; Observational Study; Outcome; Outcome Study; Participant; Patient Self-Report; Pattern; Physical Function; Plants; Plasma; Play; Pragmatic clinical trial; Prevention; Principal Investigator; Production; Protein Biosynthesis; Proteins; Public Health; Randomized; Recommendation; Recommended Dietary Allowance; Regression Analysis; Research; Resistance; Risk; Role; Sampling; Serum; Shapes; Source; Statistical Models; Training; Walking; Woman; absorption; age related; age-related muscle loss; base; career; career development; cohort; dietary; dietary guidelines; disability; dysbiosis; frailty; functional disability; functional loss; gut dysbiosis; gut health; gut inflammation; gut microbiome; gut microbiota; health data; healthy aging; improved; improved functioning; improved mobility; inflammatory marker; insight; men; microbial; microbial composition; microbiome composition; muscle form; nutrition; nutritional epidemiology; precision nutrition; prevent; protein distribution; protein intake; protein metabolism; response; skills; walking speed

This K01 application is for Dr. Samaneh Farsijani to establish a research career in Nutritional Epidemiology and acquire skills to integrate omics (gut microbiome) and non-omics (dietary intake) data towards her long-term goal in “Precision Nutrition” to develop age-specific dietary recommendations, replacing the current one-size-fits-all approach, to promote healthy aging. The proposal is derived from the candidate’s extensive training in nutrition and interdisciplinary research background in biology and epidemiology. The proposed training goals are directed to advance candidate’s skills in 1) aging & nutritional epidemiology; 2) advanced biostatistics; 3) gut microbiome; and 4) career development. Acquired skills will be applied toward the proposed scientific goal to determine the relationships between protein intake, gut microbiome, inflammation, and mobility loss in older adults. Aging is associated with inefficient utilization of dietary proteins, due to anabolic resistance, which potentially leads to functional losses. Also, up to 50% of US older adults fail to meet the Recommended Dietary Allowance (RDA) for protein (0.8 g/kg body weight/d). Therefore, a higher protein intake, above the RDA (1.0-1.2 g/kg/d), has been suggested to compensate for changes in protein metabolism and to maintain muscle health in aging. However, this strategy has not been incorporated into dietary guidelines due to inconclusive evidence from small and short- term studies, which were unable to show the underlying mechanisms and causal relationships between protein intake and mobility function in older adults. Gut dysbiosis (i.e., changes in gut microbiome) and inflammaging (i.e., low-grade chronic inflammation in aging) have been linked to frailty in older adults. Since diet plays a key role in shaping the gut microbiome and inflammation, it may be speculated that the effects of protein intake on mobility function are mediated through alterations of dysbiosis and inflammaging. Our central hypotheses are: i) high protein intake reduces the risk of mobility limitation by ameliorating inflammaging; ii) different protein intake metrics are independently associated with gut microbiome and inflammaging; and iii) gut dysbiosis is associated with mobility impairment in older adults. This proposal will leverage data from Health, Aging & Body Composition (Health ABC), and Study of Muscle, Mobility & Aging (SOMMA) cohorts to address three Aims: Aim 1: To simulate a pragmatic clinical trial using the Health ABC cohort to determine i) the effect of protein intake on the risk of mobility limitation, and ii) its causal mediation by amelioration of inflammaging. Aim 2: a) To characterize the associations between different metrics of protein intake (i.e., quantity, source and within-day distribution pattern), gut microbiome composition, and fecal metabolites; and b) to determine the association between gut dysbiosis and inflammaging in SOMMA. Aim 3: To determine the cross-sectional associations between gut microbial composition and fecal metabolites with mobility (i.e., gait speed) in older adults from SOMMA. This project will broaden our insights into the influence of protein intake, as a modifiable factor, on gut microbiome, inflammaging, and muscle health in aging with the ultimate goal to drive age-specific dietary advice.

此K01应用程序是针对Samaneh Farsijani博士建立营养流行病学和 获取将OMICS（肠道微生物组）和非词（饮食摄入量）数据整合到她的长期目标的技能 在“精确营养”中开发特定年龄的饮食建议，取代当前的一定程度。 方法，以促进健康的衰老。该提案来自候选人的广泛营养培训 以及生物学和流行病学的跨学科研究背景。拟议的培训目标是指导的 提高候选人在1）衰老和营养流行病学方面的技能； 2）高级生物统计学； 3）肠道微生物组； 4）职业发展。获得的技能将用于拟议的科学目标，以确定 蛋白质摄入量，肠道微生物组，注射和迁移性丧失之间的关系。衰老是 由于合成代谢性的耐药性，与饮食蛋白效率低下相关，这可能导致 功能损失。此外，我们中有多达50％的老年人无法满足推荐的饮食津贴（RDA） 用于蛋白质（0.8 g/kg体重/d）。因此，较高的蛋白质摄入量高于RDA（1.0-1.2 g/kg/d） 建议弥补蛋白质代谢的变化并维持衰老中的肌肉健康。然而， 由于小规模和短期的证据，该策略尚未纳入饮食指南中 术语研究无法显示蛋白质之间的基本机制和因果关系 老年人的摄入量和流动性功能。肠道营养不良（即肠道微生物组的变化）和炎症 （即衰老中的低度慢性炎症）与老年人的脆弱有关。由于饮食扮演钥匙 在塑造肠道微生物组和注射中的作用，可以推测蛋白质摄入的作用 迁移率功能是通过改变营养不良和炎症的改变来介导的。我们的中心假设是： i）高蛋白摄入量通过改善炎症来降低迁移率限制的风险； ii）不同的蛋白质 摄入指标与肠道微生物组和炎症独立相关。 iii）肠道营养不良是 与老年人的流动障碍有关。该建议将利用健康，衰老和身体的数据 组成（健康ABC）和肌肉，流动性和衰老（SOMMA）的研究以解决三个目标： 目标1：使用健康ABC队列模拟务实的临床试验以确定i）蛋白质的影响 摄入流动性限制的风险，ii）通过改善炎症的因果介导。目标2：A） 为了表征蛋白质摄入量不同指标（即数量，来源和日期）之间的关联 分布模式），肠道微生物组组成和粪便代谢产物； b）确定关联 在肠道营养不良和Somma炎症之间。目标3：确定横截面关联 在肠道微生物组成和具有迁移率的粪便代谢物（即步态速度）之间 索玛。该项目将扩大我们对蛋白质摄入的影响的见解，作为一个可修改因素，对肠道的影响 衰老中的微生物组，炎症和肌肉健康，是推动特定年龄饮食建议的最终目标。