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Tubular senescence and proliferative capacity of the aging kidney

衰老肾脏的肾小管衰老和增殖能力

基本信息

批准号：
10397142
负责人：
Monica Chang-Panesso
金额：
$ 15.05万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10397142
关键词：
Acute Acute Renal Failure with Renal Papillary Necrosis Address Advisory Committees Aging Alzheimer&apos s Disease American Apoptosis Atrophic Attention Biology of Aging CDKN2A gene Cell Aging Cell Cycle Arrest Cell Proliferation Cells Censuses Chronic Kidney Failure Clinical Clone Cells Communities Data Defect Development Disease Elderly Epithelial Epithelial Cell Proliferation Epithelial Cells FOXM1 gene Fatal Outcome Fibrosis Gene Expression Profile Goals Impairment In Vitro Incidence Injury Injury to Kidney Kidney Knock-in Mouse Label Laboratories Medical Mentorship Molecular Morphology Mus Natural regeneration Nephrology Organ Parkinson Disease Pathogenesis Persons Phenotype Physicians Play Population Predisposition Proliferating Recording of previous events Recovery Regenerative response Reporting Repression Resources Risk Risk Factors Role Scientist Site Techniques Testing Therapeutic Intervention Time Training Training Programs Tubular formation United States Universities Washington World Health Organization age group age related aged aging population biomarker panel career career development clinically relevant experience human old age (65+)in vivo injured insight interest member new therapeutic target novel overexpression prevent profibrotic cytokine repaired reparative capacity response senescence transcription factor trend

项目摘要

PROJECT SUMMARY/ABSTRACT Acute kidney injury (AKI) and chronic kidney disease (CKD) are much more common among the elderly, and the aging population in the United States is rising rapidly. According to data from US Census Bureau, there will be about 72 million people 65 and older by 2030, about one in every five Americans, this is more than twice their number in 2000. The medical community is already seeing a high incidence of acute kidney injury in the elderly population and it is expected that this will continue to rise with an increase in this age group. This concerning trend; however, has received little attention despite the detrimental and potential fatal outcomes associated with an episode of AKI, especially in this age group. The purpose of this study is to explore the mechanisms that underlie the decrease reparative response in the aging kidney after injury with a special focus on tubular senescence and epithelial cell proliferation. The specific aims of this proposal include: 1) Define the proliferative capacity of young vs. old proximal tubule cells by clonal analysis of dedifferentiated cells, 2) Assess and characterize proximal tubule senescence in young vs. old kidneys after injury, and 3) To determine if augmenting the proliferative response via transient overexpression of the transcription factor Foxm1 leads to enhance renal recovery. Through these aims, our goal is to get an understanding of the biology of the aging kidney in order to guide the quest for therapies to prevent, ameliorate or cure acute kidney injury in the elderly or its progression to chronic kidney disease. This proposal outlines a 5-year training program to provide support and guidance towards the applicant long-term career goal of becoming an independent physician-scientist studying the molecular mechanisms that impair the regenerative response after acute kidney injury in aging. The plan consists of coursework, training in new laboratory techniques and guidance from Dr. Benjamin Humphreys, Chief of Division of Nephrology at Washington University, and members of the advisory committee who have a diverse wealth of expertise and mentorship experience. The proposed studies try to address a highly relevant clinical problem such as AKI in the elderly while providing resources for the applicant's career development.

项目总结/文摘