常山酮基于调控自噬抵抗衰老作用和机制的研究

衰老与许多衰老性疾病的发生和发展关系密切。衰老在挑战个人、家庭和社会经济和心理负担能力的同时，更是一个现今医学界面临急需解决的难题。衰老，其本质是衰老细胞的累积，提示清除和减少衰老细胞的累积或成为抗击衰老研究的主要方向。自噬作为一种高保守的降解机制，能有效的减少和抑制衰老细胞的产生和累积，然而自噬水平在衰老模型中出现了明显的下降，通过上调衰老时期的自噬水平有效的延缓衰老疾病和运动功能障碍的发生和发展，提示上调自噬水平或可成为抗击衰老的重要机制。常山酮是一种从中药常山中分离得到的喹唑啉酮生物碱，其作用机制因细胞类型或细胞内的信号环境不同而出现显著差异。我们前期的研究发现，常山酮能通过上调自噬水平显著延长线虫的寿命，然而常山酮在抗击衰老过程中的作用和机制则需要更加深入的研究，且迄今为止国内外尚未有类似的研究报道。本项目拟从细胞、线虫和小鼠中探索常山酮上调自噬延缓衰老的能力和作用机制

Aging is considered to associate with various types of senile diseases, including cancer, hypertension, diabetes, cardiovascular disease, arthritis, chronic obstructive pulmonary, Alzheimer's disease and Parkinson's disease, the manifestation and progression of which show a positive correlation with age. Nowadays, senescence still remains a challenge to modern medical science, not only because of heavy finance and mentality burden pushed upon individual, family and society, but also causing diseases together with psychological problems which are contradicted with the expectance of health life expansion and high quality of elderly lives. Fundamentally, the accumulation of senescent cells laid the ground of senescence which refers to an irreversible process involving the degradation and disturbance of multi-tissues and multi-organ function, suggesting clearance and reduction of senescent cells may be becoming the target of anti-aging research. Autophagy is a highly conservative degradation mechanism, can effectively reduce and inhibit the generation and accumulation of senescent cells, however, previous researches showed the level of autophagy decline following with aging, suggesting rising the autophagy level may be the key mechanism to combat aging in turn to delay the occurrence and development of age-related diseases. Halofuginone is a quinazoline alkaloid isolated from Chinese herb Dichroa febrifuga Lour. Surprisingly, the function of halofuginone differs significantly from cell to cell depending on the cell types or environments within the cell. Our research found that halofuginone significantly extends the lifespan of C.elegans by increasing the level of autophagy. However, the target and mechanism of halofuginone regard to autophagy level rising still require more detailed research. This project intends to explore the ability and mechanism of halofuginone to up-regulate autophagy resulting in anti-aging effects through an experiment designed in mammalian cells, C.elegans and mice.