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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：
10681468
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/10681468
关键词：
Acceleration 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 Disparity Environment Environmental Risk Factor Exhibits Faculty Female Gene Expression Gene Expression Regulation Genetic Transcription Genomics Glean Goals Health Hippocampus Human Hypothalamic structure Immune Immune response Incidence Individual Inflammation Inflammatory Inflammatory Response Intervention 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 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 poor health outcome 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.

项目总结