Metabolism and Translational Science Core

代谢与转化科学核心

基本信息

批准号：
10631863
负责人：
CHRISTIAAN LEEUWENBURGH
金额：
$ 24.52万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10631863
关键词：
Aging American Ancillary Study Autophagocytosis Biochemical Biological Biological Markers Biology Blood Blood capillaries Brain Cell Aging Cell Separation Cell physiology Cells Circadian Dysregulation Clinical Research Clinical Sciences Coenzymes Collaborations Complementary DNA Complex Consultations Country DNA DNA copy number Data Deterioration Disease Elderly Electron Transport Enzyme-Linked Immunosorbent Assay Epigenetic Process Fatty acid glycerol esters Florida Freezing Future Gene Expression Profiling Genomic Instability Genomics Geroscience Goals Homeostasis Human Human Resources Immunoassay Impairment Inflammation Infrastructure Intervention Knowledge Laboratories Leukocytes Longevity Measures Metabolic Pathway Metabolism Methodology Mitochondria Mitochondrial DNA Molecular Monitor Muscle Mutation NADH NADP Nicotinamide adenine dinucleotide Nuclear Organelles Pathway interactions Pattern Physical Function Physiological Processes Pilot Projects Plasma Principal Investigator Protein Analysis Proteins Proteomics Qualifying RNA Reaction Reader Recording of previous events Research Research Personnel Research Support Resolution Resources Respiration Respiratory physiology Sampling Scientist Sensory Serum Services Spirometry Techniques Technology Time Tissue Sample Tissues Touch sensation Translational Research Universities Vertebral column Western Blotting Whole Blood age related analytical tool austin biobank biomarker selection circadian pacemaker cognitive function design detection of nutrient detection platform education research enzyme activity exhaustion healthy aging high standard high throughput analysis innovation interest metabolomics mitochondrial dysfunction nanoimmunoassay novel pre-clinical proteostasis research study senescence specific biomarkers stem cells telomere transcriptomics

项目摘要

Summary The University of Florida (UF) Older Americans Independence Center (OAIC) supports the overall theme of “promotion of mobility and independence.” The Metabolism and Translational Science Core (RC2), in collaboration with our other UF OAIC cores, supports biochemical analyses for preclinical, human interventional, or observational clinical studies. By measuring a selected set of biomarkers, we can determine how targeted interventions influence the rate of aging, as well as loss of mobility and independence. This core thereby provides the support for the Research Education Core (REC) Scholars and pilot study investigators. Aging and disease feature progressive deterioration of various physiological and metabolic processes. This is associated with altered functions or contents of protein, RNA, and DNA, which provide biomarkers to monitor aging. Multiple pathways and domains have been associated with aging, such as genomic instability (including telomere attrition, mutations, and deletions); epigenetic alterations; loss of proteostasis (including dysfunctional autophagy); deregulated nutrient sensing; mitochondrial (Mt) dysfunction; inflammation and cellular senescence; stem cell exhaustion, disrupted circadian clock rhythms; and dysfunctional nicotinamide adenine dinucleotide (NAD+) homeostasis. The specific analyses of protein, RNA, and DNA biomarkers that this core will provide are related to major biological and metabolic pathways known to regulate aging and focus on: (i) Mt function; (ii) inflammation and senescence; (iii) autophagy; (iv) circadian clock biology; and (v) NAD+ homeostasis. We use innovative analytical tools and standard high-throughput analysis to determine the fundamental biological mechanisms of aging. The Metabolism and Translational Science Core (RC2) supports the overarching hypothesis that knowledge of specific protein, RNA, and DNA biomarkers, as well as measurements of metabolism of isolated mitochondria and white blood cells (WBCs), are critical for understanding the trajectory of healthy aging and the underlying biological causes of mobility loss. We will support extraction of proteins, RNA, and DNA; analysis of biomarkers; isolation of cells (WBCs) and organelles (mitochondria); and assessments of Mt function. RC2 will provide investigators across the OAIC Cores and REC Scholars with established methodologies; scientific data; infrastructure; highly qualified personnel; and consultative and collaborative expertise. We have a rich history of completing studies for REC Scholars and senior investigators at UF, as well as scientists around the country. RC2 pursues the following aims: Aim 1: To support protein, RNA, and DNA isolation and analysis of specific biomarkers of aging. Aim 2: To support analysis of Mt respiration, Mt enzyme activities, and NAD coenzymes. Aim 3: To facilitate and provide consultation on analyses and sample storage, and collaborate synergistically with the other OAIC cores to pursue the common OAIC theme of promotion of mobility and independence.

概括佛罗里达大学（UF）老年人独立中心（OAIC）支持整体 “促进流动性和独立性”的主题。代谢和转化科学核心（RC2），与我们的其他UF OAIC核心合作，支持临床前，人类的生化分析介入或观察性临床研究。通过测量选定的生物标志物，我们可以确定有针对性的干预措施如何影响衰老率以及移动性和独立性的丧失。这个核心因此，为研究教育核心（REC）学者和试点研究人员提供了支持。衰老和疾病具有各种物理和代谢过程的逐步恶化。这与蛋白质，RNA和DNA的功能变化或内容有关，这些功能或DNA提供了生物标志物至监视老化。多个途径和域与衰老有关，例如基因组不稳定性（包括端粒损耗，突变和缺失）；表观遗传改变；失去蛋白抑制性（包括功能失调的自噬）；放松管制营养感；线粒体（MT）功能障碍；发炎和细胞感应；干细胞耗尽，昼夜节律的破坏；和功能失调的烟酰胺腺嘌呤二核苷酸（NAD+）稳态。蛋白质，RNA和DNA生物标志物的特定分析该核心将提供的与已知调节衰老的主要生物学和代谢途径有关在：（i）MT功能；（ii）炎症和敏感；（iii）自噬；（iv）昼夜节律生物学；和（v）NAD+稳态。我们使用创新的分析工具和标准的高通量分析确定衰老的基本生物学机制。新陈代谢和转化科学核心（RC2）支持总体假设，即特定蛋白，RNA和DNA生物标志物的知识为以及分离的线粒体和白细胞（WBC）代谢的测量至关重要了解健康衰老的轨迹和迁移率丧失的潜在生物学原因。我们将支持蛋白质，RNA和DNA的提取；分析生物标志物；分离细胞（WBC）和细胞器（线粒体）；和MT功能的评估。 RC2将为调查人员提供具有既定方法的OAIC核心和REC学者；科学数据；基础设施;高素质人员;以及协商和协作专业知识。我们拥有完成Rec研究的悠久历史 UF的学者和高级调查员以及全国各地的科学家。 RC2追求以下目的：目标1：支持蛋白质，RNA和DNA分离和分析衰老的特定生物标志物。目标2：支持MT呼吸，MT酶活性和NAD辅酶的分析。目标3：促进并提供有关分析和样品存储的咨询，并协同协作有了其他OAIC核心，追求促进流动性和独立性的共同的OAIC主题。