Identifying Regulators of Cellular Aging that can Prevent Alzheimer's Disease

识别可以预防阿尔茨海默病的细胞衰老调节因子

• 批准号: 10624244
• 负责人: Benjamin Jacob Doranz
• 金额: $ 8.9万
• 依托单位: INTEGRAL MOLECULAR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10624244
• 关键词: Abbreviations; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Antibodies; Astrocytes; Biological Assay; Biological Markers; Biological Models; Biological Products; Cell Aging; Cells; Cellular Stress; Chronic Disease; Clinical Trials; DNA Damage; DNA Methylation; DNA Repair; Disease; Drug Targeting; Engineering; Epigenetic Process; Future; Gene Expression; Generations; Genes; Genomic Instability; Health; Human; Internal Ribosome Entry Site; Libraries; Link; Longevity; Marketing; Membrane; Methods; Microglia; Mitochondria; Modeling; Molecular Conformation; Monitor; Nutritional; Outcome; Oxidative Stress; Pathway interactions; Patients; Pharmaceutical Preparations; Phenotype; Plasmids; Prevention; Process; Proteins; Proteome; Reactive Oxygen Species; Reporter; Source; T-Lymphocyte; Technology; Testing; Therapeutic; Therapeutic Intervention; Transfection; Translating; Virus Receptors; Work; cell age; cell growth regulation; cell preparation; comorbidity; expression vector; gene product; gene therapy; healthspan; immune checkpoint; improved; lentivirally transduced; manufacture; metaplastic cell transformation; methylation biomarker; mitochondrial dysfunction; mouse model; new therapeutic target; oxidation; pharmacologic; phase 2 study; prevent; programs; proteostasis; stem cell biology; stem cells; targeted treatment; telomere; therapeutic target; timeline; transcription factor

ABSTRACT Aging is the leading risk factor for Alzheimer’s Disease (AD) and many other chronic diseases, with more than 6.5 million cases of AD in the US. Regulating or slowing cellular aging, particularly in microglia and astrocytes that regulate neuroimmunity, would have a major impact on the treatment of AD, but the proteins that control cellular aging processes are poorly understood. Cellular aging has been characterized into 9 “hallmarks” or phenotypes that define aged cells. Most hallmarks are a result of cellular stress, such as DNA damage and oxidation, and are inter-related in both their causes and outcomes. The cellular aging process is linked to dramatically altered gene expression, which is largely controlled by transcription factors (TFs). Longevity studies between species also suggest that TF activity can define the rate of aging. We hypothesize that TFs can modulate cellular aging and that identifying the TFs that play a role in aging processes will enable an entirely new generation of therapeutic targets with the potential to treat, delay, and possibly even prevent AD. The discovery of TFs that can improve the lifespan of patients would have a profound impact on the prevention and treatment of AD and many other diseases.

摘要