Age-Related Dysbiosis and Physical Resilience

本提案是针对RFA-AG-20-030《微生物组与衰老：对健康和 疾病。“该项目通过首次评估肠道微生物群对RFA的影响来解决这个问题 老鼠的体能恢复能力。利用一支在两个领域都有丰富经验的多学科团队 微生物组和衰老科学，我们将解决以下具体目标：1)确定 肠道微生物群与年龄相关的身体韧性下降有关，2)隔离老年人的影响 肠道微生物区系对弹性反应的影响，以及3)确定体育锻炼、膳食纤维和 它们的结合，以及微生物组和SCFA功能能力的相关变化，对物理 年长动物的韧性。恢复力的定义是身体功能的恢复，证明是 一组复合的功能测量，我们还将评估微生物组与所谓的 生物介质包括胰岛素敏感性、肠道屏障功能、身体成分以及局部肠道和 全身炎症。预期影响：该项目将解决老年科学的物理概念 通过提供第一个将韧性与肠道微生物群联系起来的数据，我们发现了一种新的抗逆性。这个项目利用了一个 我们团队的工作历史，并由一个概念模型驱动，该模型假设肠道中与年龄相关的变化 微生物区系驱动机体免疫功能和能量利用的变化，最终有助于 炎症和身体成分的变化，损害了机体恢复身体功能的能力 生理挑战。最终，这个项目充分利用了人们对肠道重要性的最新认识 微生物群对健康和疾病的影响，旨在向我们的长期目标迈出实质性的一步 促进对身体复原力的了解，最终制定在年中提高复原力的策略 晚年生活。

This proposal is submitted in response to RFA-AG-20-030 “Microbiome and Aging: Impact on Health and Disease.” The project addresses this RFA by evaluating for the first time the impact of the gut microbiome on physical resilience in mice. Leveraging a multidisciplinary team with extensive experience in both the gut microbiome and aging science, we will address the following specific aims: 1) Determine the extent to which the gut microbiome is connected to age-related declines in physical resilience, 2) Isolate the effects of the aged gut microbiota on resilience responses, and 3) Determine the impact of physical exercise, dietary fiber, and their combination, and associated changes in the microbiome and SCFA functional capacity, on physical resilience in older animals. Resilience will be defined by recovery in physical function, evidenced by a composite set of function measures, and we will also evaluate relationships of the microbiome to purported biologic mediators including insulin sensitivity, gut barrier function, body composition, as well as local gut and systemic inflammation. ANTICIPATED IMPACT: This project will address the Geroscience concept of physical resilience by providing the first data relating resilience to the gut microbiome. This project capitalizes on a history of work by our group and is driven by a conceptual model which posits that age-related changes in gut microbiota drive changes in organism immune function and energy utilization, ultimately contributing to inflammation and body composition changes that impair organismal ability to recover physical function after physiologic challenge. Ultimately this project leverages recent understanding of the importance of the gut microbiome to health and disease and is designed to provide a substantial step toward our long-term goal of advancing understanding of physical resilience to ultimately devise strategies for improving resilience in mid- to late-life.