The aging stem cell niche

衰老干细胞生态位

• 批准号: 10631903
• 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/10631903
• 关键词: Address; Affect; Age; Aging; Anatomy; 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 satellite cell; 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; cell age; cell replacement therapy; disability; genetic manipulation; germline stem cells; human stem cells; in vivo; insulin signaling; model organism; 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; 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. !

项目摘要摘要 好了！ 与年龄相关的干细胞功能障碍被认为是导致健康、组织退化的原因 退化和癌症。干细胞利基是维持干细胞所必需的，而且 壁龛和干细胞都会老化。潜在地逆转干细胞的有害影响 衰老和预测干细胞等再生医学策略 更新换代将受到老化利基环境的影响，我们需要了解 老化如何影响整个单位，包括利基市场。局部干细胞在物理上的位置 与干细胞相互作用并向干细胞发出信号，而衰老可以改变这些利基-干细胞的相互作用。 然而，人们还不太清楚老化的利基市场的这些方面是如何结合在一起的 与年龄相关的干细胞衰退，也不知道如何逆转它们以潜在地恢复活力 老化的干细胞。该项目结合了成像、分子遗传学和细胞 已建立的衰老生物学模式生物--线虫的生物学途径 它有一个解剖学上定义明确且可接近的利基环境，支持生殖系干细胞 细胞。因此，该项目对生殖老龄化也有影响。该项目将 阐明衰老如何影响利基及其反应的干细胞，发现 驱动生态位衰老的分子机制，并决定生态位的潜力 使干细胞恢复活力的手法。此外，它还将解决这一利基茎如何 系统与全身性胰岛素老化途径的一个新分支整合在一起 先前被认为与该系统中的干细胞老化有关。 好了！