Role of transposon regulation in the negligible senescence of S. mediterranea

项目总结 成体干细胞功能的进行性下降是年龄相关疾病发生的主要因素。 条件。考虑到整个人口的老龄化，确定延长 干细胞健康是非常重要的。对短期模型系统的研究已经确定了许多潜力 干细胞维持的限制因素，但一直无法阐明干细胞是否以及如何 衰老是完全可以避免的。我们将利用可以忽略不计的衰老系统地中海链霉菌来揭示 这种动物维持干细胞健康的能力背后的调节似乎是无限期的。我们之前 研究发现，脊椎动物干细胞对转座子具有双层保护作用，而较短的 活的分化细胞只保留一层防御层，这表明转座子可能是一个重要的 对干细胞维护的威胁。此外，失去转座子沉默会导致这些疾病的迅速致死。 长寿动物。这个项目着重于转座子沉默和染色质紧致在 脊椎动物组织的抗衰老表型。我们打算利用我们最近发现的刻板印象 与年龄相关的标记物在脊椎动物分化细胞中的作用 脊椎动物衰老的进展。这项提案的目标1试图阐明转座子水平的变化 染色质调节可以改变脊椎动物分化组织的衰老速度。目标2解决了 转座子相关的各种途径在无限期维持浮游动物干细胞中的作用。目标3将 确定一种扁平动物组织类型的寿命与其对 转座子。此外，染色质修饰中与年龄相关的变化的基因组位置将是 地址。 这个项目将为一个老化程度微乎其微的系统的工作原理提供新的见解。对这一概念的理解 它在长期维持其活跃分裂的干细胞群体中使用的机制将提供 寻求扩展人类干细胞健康战略的新途径。

PROJECT SUMMARY The progressive decline in the function of adult stem cells is a major factor in the development of age-related conditions. Considering the increasing age of the overall human population, identifying strategies to prolong stem cell health is of major importance. Study of short-lived model systems has identified many potential limiting factors in the maintenance of stem cells, but has been unable to elucidate whether and how stem cell aging could be avoided altogether. We will leverage the negligibly senescent system S. mediterranea to reveal the regulation underlying this animal’s ability to maintain stem cell health seemingly indefinitely. We previously found that planarian stem cells employ a double layer of protection against transposons, whereas the shorter- lived differentiated cells retain only a single defense layer, suggesting that transposons could be a significant threat to stem cell maintenance. Further, loss of transposon silencing leads to rapid lethality in these otherwise long-lived animals. This project focuses on the role of transposon silencing and chromatin compaction in the resistance to aging phenotypes of planarian tissues. We intend to leverage our recent finding of stereotypic age-related markers in planarian differentiated cells to determine the role of various pathways in the progression of planarian aging. Aim 1 of this proposal seeks to elucidate whether changes in transposon levels or in chromatin regulation can change the rate of aging in planarian differentiated tissues. Aim 2 addresses the role of various transposon-related pathways in the indefinite maintenance of planarian stem cells. Aim 3 will determine whether there is a correlation between the lifespan of a planarian tissue type and its control of transposons. Furthermore, the genomic locations of age-related changes in chromatin modifications will be addressed. This project will provide new insights in the workings of a negligibly senescent system. Understanding of the mechanisms it employs in the long-term maintenance of its actively dividing stem cell population will provide new avenues to pursue in search for strategies to extend human stem cell health.