Social and dietary modifiers of neuroinflammation and aging

神经炎症和衰老的社会和饮食调节剂

基本信息

批准号：
10525952
负责人：
Kenneth Lyu Chiou
金额：
$ 12.17万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
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：
2022-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10525952
关键词：
Acute Address Adult Affect Age Aging Alcoholism Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Amygdaloid structure Animal Model Attenuated Biological Biology Brain Brain region Buffers Cells Characteristics Chronic Chronic Disease Chronic stress Cognitive Collaborations Dementia Development Diet Dietary Intervention Disease Environment Environmental Risk Factor Exhibits Faculty Female Gene Expression Gene Expression Regulation Genetic Transcription Genomics Glean Goals Health Hippocampus (Brain)Human Hypothalamic structure Immune Immune response Incidence Individual Inflammation Inflammatory Inflammatory Response Intervention Lead Link Longevity Macaca Mammals Measurement Mediterranean Diet Mentors Microglia Modeling Molecular Nerve Degeneration Neurodegenerative Disorders Neurologic Neurosciences Nutritional Obesity Outcome Pathology Pathway interactions Phenotype Physiological Play Population Population Control Prefrontal Cortex Primates Psychophysiology Research Role Sampling Shapes Smoking Social Behavior Social Environment Social Gradients Social Sciences Social outcome Social status Stimulus Stress System Testing Training Training Activity Trauma Unhealthy Diet Up-Regulation Variant Women&apos s Group Work adverse outcome age related aging brain aging population base behavior influence biological adaptation to stress brain cell brain health career cell type cohort design dietary entorhinal cortex experience genome-wide human model human old age (65+)inflammatory modulation insight middle age mortality mortality risk neuroinflammation neuropathology nonhuman primate programs resilience response single-cell RNA sequencing social social adversity social influence social relationships social stress social stressor stimulus processing study population therapy development western diet

项目摘要

PROJECT SUMMARY Social experiences shape the health and longevity of humans and other social mammals. Social adversity in humans and in social nonhuman primates is associated with higher mortality and poorer health. One prevailing explanation is that chronic stress dysregulates the physiological response to stress, resulting in a chronic inflammatory phenotype that accelerates aging and is associated with chronic neurodegenerative diseases such as Alzheimer's disease. These inflammatory outcomes overlap with those influenced by diet. In comparisons of two prevailing diets that differ in nutritional composition—the Western and Mediterranean diets—Western diets are associated with not only poorer health and an increased risk of Alzheimer's disease and other dementias, but also a chronic inflammatory phenotype. These characteristics raise the question of how diet and social experiences interact to influence aging and health. The objective of the proposed study is to identify the molecular mechanisms that link social adversity and diet to the stress response and inflammation. If the inflammatory outcomes of social adversity and diet share some common molecular mechanisms, I hypothesize that the diet can mitigate age-accelerating phenotypes in the brain by modulating neuroinflammatory responses to social adversity. To test this hypothesis, I will leverage the advantages of studying female macaques, which are well-established animal models of human social behavior, aging, and chronic disease. I propose a two-pronged approach that combines studies of free-ranging macaques spanning the entire adult lifespan (Aim 1) with experimental manipulations of diet in a middle-aged macaque cohort (Aims 2 and 3), thus yielding insights into the relationships between stress, neuroinflammation, and aging in an integrated model. In both contexts, I will combine genome-wide gene expression measurements to characterize the genomic pathways associated with social adversity and diet. Insights gleaned from the free-ranging population (Aim 1) will be used to characterize how social adversity and diet interact to influence neurodegeneration and brain aging (Aims 2-3), and to understand the role of key cell types, including microglia (Aim 3). At its conclusion, this project will yield a detailed understanding of how social adversity and diet affect gene regulation and neuroinflammation in the aging brain, and how diet interventions can buffer against the health consequences of chronic social stress. Together, these results will advance our understanding of the mechanisms through which diet or social adversity impact cognitive and neurological resilience in the aging population. In addition, the proposed program of mentored training activities will allow me to develop a strong, independent research career in aging, focused on the nexus of aging, social behavior, neuroscience, and genomics.

项目概要社会经历塑造了人类和其他社会哺乳动物的健康和寿命。在人类和社会性非人类灵长类动物中，这种疾病与较高的死亡率和较差的健康状况有关。普遍的解释是，慢性压力会失调对压力的生理反应，导致加速衰老并与慢性神经退行性疾病相关的慢性炎症表型这些炎症结果与饮食影响的疾病有重叠。两种营养成分不同的流行饮食——西方饮食和地中海饮食的比较饮食——西方饮食不仅会导致健康状况不佳，而且会增加患阿尔茨海默病的风险和其他痴呆症，而且还有慢性炎症表型，这些特征提出了问题。饮食和社会经历如何相互作用影响衰老和健康。拟议研究的目的是确定将社会逆境与饮食对压力反应和炎症的影响如果社会逆境和饮食共同导致炎症结果。一些常见的分子机制，我认为饮食可以减轻加速衰老的表型为了检验这个假设，我将利用调节神经炎症反应来调节大脑对社会逆境的反应。研究雌性猕猴的优势，雌性猕猴是人类社会公认的动物模型我提出了一种结合自由放养研究的双管齐下的方法。跨越整个成年寿命的猕猴（目标 1），并在中年人中进行饮食实验控制猕猴队列（目标 2 和 3），从而深入了解压力、在这两种情况下，我将结合全基因组基因。表达测量来表征与社会逆境和饮食相关的基因组途径。从自由放养的人群中收集的见解（目标 1）将用于描述社会逆境和饮食相互作用影响神经退行性变和大脑衰老（目标 2-3），并了解关键细胞的作用类型，包括小胶质细胞（目标 3）。最后，该项目将详细了解社会逆境和饮食如何影响基因衰老大脑中的调节和神经炎症，以及饮食干预如何缓冲健康这些结果将共同促进我们对长期社会压力的后果的理解。饮食或社会逆境影响衰老过程中认知和神经恢复能力的机制此外，拟议的指导培训活动计划将使我能够培养强大的、衰老领域的独立研究生涯，重点关注衰老、社会行为、神经科学和基因组学。