5-羟色胺调控线虫寿命精细机制探究

Aging process is characterized with physiological function decline and a number of aging-associated diseases, ultimately leading to death. Exploration of the cellular and molecular mechanisms underlying aging and longevity has been the hotspot of current scientific research, which is critical for anti-aging therapy as well as promoting longevity. It has been reported that serotonin performed profound modulation effects on aging and longevity, however, the functional mechanisms are far away from clear. Our preliminary work confirmed that increase the activity of serotoninergic neurons would be able to promote C.elegans lifespan. In addition, our data suggested that serotonin receptor SER-7 could regulate the transcriptional activity of master longevity modulator DAF-16/FOXO. Therefore, this project is aiming at investigating the detailed mechanisms underlying longevity modulation effect of serotonin in C.elegans, uncovering the regulatory function of serotoninergic neurons on C.elegans lifespan and determining the downstream pathways for serotonin receptors to modulate longevity in C.elegans with genetics, cellular and molecular biology and imaging analysis tools. Furthermore, this project will detect the effects of potential agonists and antagonists of serotonin receptors on C.elegans lifespan and elucidate the underlying molecular mechanisms, offering novel targets for anti-aging research.

衰老过程伴随着多种生理功能的下降及衰老相关疾病的发生，最终导致生物个体的消亡。对衰老及长寿调控机制的探究是当下科学研究的热点，对抗衰老促长寿的实现具有重要的意义。研究发现，5-羟色胺可以有效地调节生物个体的衰老及长寿，但其具体分子作用机理远没有得到清晰地阐述。我们的前期实验数据显示，增强5-羟色胺神经元活性可以有效地延长线虫的寿命，同时5-羟色胺受体SER-7可以显著地调节寿命调控因子DAF-16/FOXO的活性。有鉴于此，本课题将以线虫为模型，通过遗传学、分子与细胞生物学、成像分析等技术手段，进一步深入地探究5-羟色胺分子对线虫寿命的调控作用，揭示5-羟色胺神经元活性与线虫寿命之间的联系，确立5-羟色胺受体调控线虫寿命的分子作用网络。同时，本课题将探讨5-羟色胺受体激动剂和抑制剂对线虫寿命的调控作用，为抗衰老研究提供新的方向。

神经系统及神经递质在环境因子和遗传因子系统调控衰老及寿命的过程中起到极其重要的作用。已有的研究结果报道了5-羟色胺对线虫的寿命具有调节作用，但其具体机制还远没有得到清晰的揭示。本项目研究系统地阐述了5-羟色胺对线虫寿命调控的精细机制，发现了不同的5-羟色胺神经元具有差异性调控线虫寿命的作用；同时发现5-羟色胺在环境因子，如温度，食物等，对线虫的寿命调控过程中具有重要的作用。总的来说，本项目从分子，细胞和组织层面构建了相对完善的5-羟色胺调控线虫寿命的精细网络，为衰老及长寿相关研究奠定了新的理论依据。