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题 目: Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost
北京生命科学研究所高级研究员
时 间: 12月12日(周一)13:00-14:00
腾讯会议号: 935484552
https://meeting.tencent.com/dm/DjIhfXV2x9Ty
主持人: 韩敬东 教授
摘 要:
Twenty-nine years following the breakthrough discovery that a single-gene mutation of daf-2 doubles Caenorhabditis elegans lifespan, it remains unclear where this insulin/IGF-1 receptor gene is expressed and where it acts to regulate ageing. Using knock-in fluorescent reporters, we determined that daf-2 and its downstream transcription factor daf-16 are expressed ubiquitously. Using tissue-specific targeted protein degradation, we determined that intracellular DAF-2-to-DAF-16 signaling in the intestine plays a major role in lifespan regulation, while that in the hypodermis, neurons, and germline plays a minor role. Notably, intestine-specific loss of DAF-2 activates DAF-16 in and outside the intestine, causes almost no adverse effects on development and reproduction, and extends lifespan by 94% in a way that partly requires non-intestinal DAF-16. Consistent with intestine supplying nutrients to the entire body, evidence from this and other studies suggests that altered metabolism, particularly down-regulation of protein and RNA synthesis, mediates longevity by reduction of insulin/IGF-1 signaling.
董梦秋,北京生命科学研究所高级研究员,耶鲁大学博士,斯克利普斯研究所博士后,2007年回国,在北京生命科学研究所工作至今。董梦秋课题组以线虫为模型研究关于衰老的基础生物学问题,同时开发基于质谱的蛋白质组学技术,在两个领域都取得了突破性进展,相关文章发表在Nature、Nature Methods、Nature Communications、eLife、Aging Cell, Journal of Proteome Research、Analytical Chemistry 等期刊。课题组开发的交联肽段质谱鉴定技术是辅助解析蛋白质结构或蛋白-蛋白相互作用的有效工具,被全球很多实验室采用。在生物学方面,课题组目前的研究重点是阐明胰岛素信号通路如何调节寿命,以及通过观测线虫衰老的生物学过程回答衰老是什么、从什么阶段开始等基本问题。