The aging stem cell niche

衰老干细胞生态位

• 批准号: 10399657
• 负责人: E. Jane Albert Hubbard
• 金额: $ 34.75万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10399657
• 关键词: Address; Affect; Age; Aging; Anatomy; Animal Model; Automobile Driving; Biological; Biology of Aging; Caenorhabditis elegans; Cell Count; Cell Maintenance; Cell Volumes; Cells; Defect; Degenerative Disorder; Disease; Distal; Environment; Functional disorder; Genetic; Genetic Screening; Genetic Transcription; Germ Lines; Gonadal structure; Hematopoietic; Hermaphroditism; Human; Image; Individual; Insulin; Knowledge; Ligands; Longevity; Malignant Neoplasms; Mediating; Modeling; Molecular; Molecular Genetics; Morphology; Muscle; Natural regeneration; Organ; Output; Pathway interactions; Phenotype; Process; RNA Interference; Regenerative Medicine; Rejuvenation; Reporter; Reproduction; Role; Signal Transduction; Skin; System; Testing; Tissues; Validation; Work; age effect; age related; aged; base; cancer stem cell; cell age; cell replacement therapy; disability; genetic manipulation; germline stem cells; human stem cells; in vivo; insulin signaling; nerve stem cell; novel; prevent; progenitor; regenerative; reproductive; reproductive senescence; stem; stem cell aging; stem cell biology; stem cell function; stem cell niche; stem cell replacement; stem cells; tissue degeneration; tissue stem cells; transcriptome sequencing

Abstract Project Summary ! Age-related stem cell dysfunction is thought to contribute to diminished heath, tissue degeneration, and cancer. The stem cell niche is required to maintain stem cells, and both the niche and stem cells age. To potentially reverse deleterious effects of stem cell aging and to predict how regenerative medicine strategies such as stem cell replacement will be influenced by an aged niche environment, we need to understand how aging affects the entire unit, including the niche. Local stem cell niches physically interact with and signal to stem cells, and aging can alter these niche-stem interactions. Yet it is not well understood how these aspects of the aging niche combine to contribute to age-related stem cell decline nor how they can be reversed to potentially rejuvenate aged stem cells. This project uses a combination of imaging, molecular-genetic, and cell biological approaches in C. elegans, an established model organism for aging biology that has an anatomically well-defined and accessible niche that supports germline stem cells. Thus the project has implications for reproductive aging as well. The project will elucidate how aging impacts the niche and its responding stem cells, discover the molecular mechanisms driving niche aging, and determine the potential of niche manipulation to rejuvenate stem cells. In addition, it will address how this niche-stem system integrates with a novel branch of the systemic insulin aging pathway that was previously implicated in stem cell aging in this system. !

项目摘要 ! 与干细胞相关的干细胞功能障碍被认为是导致健康、组织 退化和癌症。需要干细胞龛来维持干细胞， 小生境和干细胞都老化。为了潜在地逆转干细胞的有害影响， 衰老和预测再生医学策略，如干细胞 更换将受到老化的生态位环境的影响，我们需要了解 老化是如何影响整个单位的，包括利基市场局部干细胞龛 与干细胞相互作用并向干细胞发出信号，衰老可以改变这些利基-干细胞相互作用。 然而，人们还不清楚老龄化利基的这些方面如何结合联合收割机做出贡献 与年龄相关的干细胞衰退，也不知道如何逆转它们， 衰老的干细胞这个项目结合了成像、分子遗传学和细胞 生物学方法在C. elegans，一种成熟的衰老生物学模式生物 它有一个解剖学上明确定义的和可访问的生态位， 细胞因此，该项目对生殖老化也有影响。该项目将 阐明衰老如何影响生态位及其相应的干细胞， 驱动生态位老化的分子机制，并决定生态位的潜力 使干细胞恢复活力此外，它将解决如何这个利基干 系统与系统性胰岛素老化途径的一个新的分支整合， 以前在这个系统中与干细胞衰老有关。 !