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.

这个K 01应用程序是博士Samaneh Farsijani建立营养流行病学的研究生涯， 获得整合组学（肠道微生物组）和非组学（饮食摄入）数据的技能，以实现她的长期目标 在“精准营养”中，制定针对不同年龄段的饮食建议，取代目前一刀切的 方法，促进健康老龄化。该建议是从候选人在营养学方面的广泛培训中得出的 生物学和流行病学的跨学科研究背景。培训目标是针对 提高候选人在1）衰老和营养流行病学; 2）先进的生物统计学; 3）肠道微生物组; （4）职业发展。获得的技能将被应用于拟议的科学目标，以确定 蛋白质摄入量，肠道微生物组，炎症和老年人活动能力丧失之间的关系。衰老是 与膳食蛋白质的低效利用有关，由于合成代谢抗性，这可能导致 功能损失。此外，高达50%的美国老年人未能达到推荐膳食津贴（RDA） 蛋白质（0.8 g/kg体重/d）。因此，高于RDA（1.0-1.2 g/kg/d）的更高蛋白质摄入量已被纳入研究范围。 建议补偿蛋白质代谢的变化，并在衰老时保持肌肉健康。然而，在这方面， 这一策略尚未纳入膳食指南，因为来自小而短的- 长期研究，无法显示蛋白质之间的潜在机制和因果关系， 老年人的摄入和活动功能。肠道生态失调（即，肠道微生物组的变化）和炎症 (i.e.,老化中的低度慢性炎症）与老年人的虚弱有关。因为饮食是 在塑造肠道微生物组和炎症中的作用，可以推测蛋白质摄入对 运动功能通过生态失调和炎症的改变来介导。我们的主要假设是： i）高蛋白质摄入通过改善炎症降低了活动受限的风险; 摄入量指标与肠道微生物组和炎症独立相关;和iii）肠道生态失调， 与老年人的行动障碍有关。该提案将利用来自健康，衰老和身体的数据 组成（健康ABC）和肌肉，流动性和衰老（SOMMA）队列的研究，以解决三个目标： 目的1：使用健康ABC队列模拟实用的临床试验，以确定i）蛋白质 摄入量对活动受限风险的影响，以及ii）通过改善炎症进行因果调节。目标2：a） 为了表征蛋白质摄入的不同度量之间的关联（即，数量、来源和日内 分布模式）、肠道微生物组组成和粪便代谢物;以及B）确定 肠道生态失调和炎症之间的联系目标3：确定横截面关联 肠道微生物组成和具有移动性的粪便代谢物之间的关系（即，步态速度）， SOMMA。这个项目将拓宽我们对蛋白质摄入量作为一个可改变的因素对肠道影响的认识 微生物组，炎症和衰老中的肌肉健康，最终目标是推动特定年龄的饮食建议。