遗传或非遗传干预下调生长激素延缓小鼠衰老的作用机制研究

Ample evidences have shown that accumulation of ageing-associated damage leads to dysregulation of many physiological and biochemical signals required for the maintenance of healthy physiological homeostasis caused ageing. It has been known that genetic mutations, diet or drug intervention affecting the production and response of growth hormone can delay aging process. However, the underlying molecular mechanisms regulating aging process are not yet clear. With the establishment and development of a variety of slow-aging models, it provides a tool for finding common cellular and systemic characters to delay aging and aging related diseases. Our preliminary study from slow-ageing mouse models including gene mutation, diet or drug intervention to cause defects of the production and response of growth hormone found that mTor signal was reduced while ATF4 was elevated in the livers and muscle. Therefore, We hypothesize that these slow-ageing models bear common physiological and biochemical characters playing important roles in delaying aging process and prolonging healthy lifespan. Therefore, this study will focus on a few slow-ageing mouse models to analyze the effect and mechanism of mTor, ATF4 and other signal pathways on anti-ageing, and to sort out the relationship between different slow-aging models and the physiological and biochemical characteristics related to aging, help to propose a new anti-aging molecular mechanisms and the identification of drug targets for prolonging healthy lifespan.

大量的证据表明随年龄增加引起的损伤累积导致维持健康肌体的稳态平衡的众多生理生化信号失调而引起衰老。已经知道通过基因的突变或非遗传表观遗传操作如饮食或药物干预影响生长激素的产生和响应，可以推迟衰老。但目前调控衰老过程的分子机制还不清楚。随着多种衰老模型的建立和发展为寻找共同的细胞和全身系统性地延缓衰老和推迟相关疾病发生的机制提供了工具。我们对基因突变、饮食限制或药物干预生长激素的产生和响应的长寿小鼠模型的进行前期研究，发现肝脏和肌肉组织 mTor信号下降和ATF4上升 。因此，我们推测基因突变或非遗传表观操作干预生长激素功能的长寿动物模型的具有共同的生理生化特征，并在延缓衰老及延长健康寿命过程起重要作用。本项目研究将有针对性地对多个延缓衰老模型进行研究和探讨， 探索mTor，ATF4和其它信号途径在推迟衰老过程中的作用机制，提出新的抗衰老机制和寻找抗衰老药物新靶点。

大量的证据表明随年龄增加引起的损伤累积导致维持健康肌体的稳态平衡的众多生理生化信号失调而引起衰老。已经知道通过基因的突变或非遗传表观遗传操作如饮食或药物干预影响生长激素的产生和响应，可以推迟衰老。但目前调控衰老过程的分子机制还不清楚。随着多种衰老模型的建立和发展为寻找共同的细胞和全身系统性地延缓衰老和推迟相关疾病发生的机制提供了工具。我们对基因突变、饮食限制或药物干预生长激素的产生和响应的长寿小鼠模型的进行前期研究，发现肝脏和肌肉组织 mTor信号下降和ATF4上升 。因此，我们推测基因突变或非遗传表观操作干预生长激素功能的长寿动物模型的具有共同的生理生化特征，并在延缓衰老及延长健康寿命过程起重要作用。本项目研究将有针对性地对多个延缓衰老模型进行研究和探讨， 探索mTor，ATF4和其它信号途径在推迟衰老过程中的作用机制，提出新的抗衰老机制和寻找抗衰老药物新靶点。