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

基本信息

批准号：
10560519
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
项目类别：
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/10560519
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 Compensation Data Diet Dietary Proteins Dietary intake Elderly Eligibility Determination Epidemiology Food Gait speed Goals Health Health Policy Immunoassay Impairment Individual Inflammaging Inflammation Inflammatory Interdisciplinary Study Interleukin-6 Knowledge Link Long-Term Effects Mass Spectrum Analysis Measures Mediating Mediation Mediator 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 Risk Reduction Role Sampling Serum Shapes Source Statistical Models Training Walking Woman absorption age related age-related muscle loss 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 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 skill acquisition skills walking speed

项目摘要

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 申请旨在让 Samaneh Farsijani 博士在营养流行病学和获得整合组学（肠道微生物组）和非组学（膳食摄入）数据以实现长期目标的技能在“精准营养”中制定针对特定年龄的饮食建议，取代目前的一刀切该提案源自候选人在营养方面的广泛培训。以及生物学和流行病学的跨学科研究背景。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) 获得的技能将应用于拟议的科学目标，以确定目标。衰老是老年人蛋白质摄入量、肠道微生物组、炎症和活动能力丧失之间的关系。由于合成代谢抵抗，与膳食蛋白质利用效率低下有关，这可能导致此外，高达 50% 的美国老年人未能达到推荐膳食摄入量 (RDA)。蛋白质（0.8 克/公斤体重/天）因此，蛋白质摄入量高于 RDA（1.0-1.2 克/公斤/天）。建议补偿蛋白质代谢的变化并在衰老过程中保持肌肉健康。由于小而短期的证据尚不明确，该策略尚未纳入膳食指南。术语研究无法显示蛋白质之间的潜在机制和因果关系老年人肠道菌群失调（即肠道微生物组的变化）和炎症。（即衰老过程中的低度慢性炎症）与老年人的虚弱有关，因为饮食起着关键作用。在塑造肠道微生物组和炎症方面的作用，可以推测蛋白质摄入量对运动功能是通过生态失调和炎症的改变来调节的。我们的中心假设是： i) 高蛋白质摄入可通过改善炎症来降低活动受限的风险；ii) 不同的蛋白质摄入量指标与肠道微生物组和炎症独立相关；并且 iii) 肠道菌群失调是该提案将利用来自健康、老龄化和身体的数据。成分 (Health ABC) 以及肌肉、活动性和衰老研究 (SOMMA) 队列旨在实现三个目标：目标 1：使用 Health ABC 队列模拟一项实用的临床试验，以确定 i) 蛋白质的作用摄入量对行动受限的风险的影响，以及 ii) 通过改善炎症来调节其因果关系。描述蛋白质摄入量不同指标之间的关联（即数量、来源和日内摄入量）分布模式）、肠道微生物组组成和粪便代谢物，以及 b）确定关联； SOMMA 中肠道菌群失调和炎症之间的关系目标 3：确定横断面关联。老年人肠道微生物组成和粪便代谢物与运动能力（即步态速度）之间的关系 SOMMA。这个项目将拓宽我们对蛋白质摄入作为可改变因素对肠道影响的认识。衰老过程中的微生物组、炎症和肌肉健康，最终目标是推动针对特定年龄的饮食建议。