衰老由遗传和环境因素共同调控，限制进食和温度变化是调控衰老的主要环境因素。限制进食对衰老影响的遗传机制已被证实。适当降低环境温度可以延缓恒温和变温动物的衰老。传统观点认为这是通过被动的热力学现象，即低温下体内各种化学反应速率减慢，而不是通过遗传机制延缓衰老的。最近，本项目合作方许献忠教授实验室发现适当降低温度可延缓线虫的衰老 （Cell., 2013)。该现象是通过温度敏感受体TRPA1启动的遗传网络完成的。 这一发现首次证明低温延缓衰老是通过遗传网络和遗传规律调控的，其具体机制还有待深入研究。本项目将以线虫为模式动物，采用RNAi筛选，研究TRPA-1如何调控低温延缓衰老的精细遗传网络和遗传机制并发现其他温度感受器, 并在小鼠及细胞模型上验证发现的相关遗传网络和遗传规律的保守性。合作双方有良好的合作基础，共同发表了2篇论文 (Cell., 2013; Cell metab.,2013）。

Aging can be modulated by both environmental and genetic factors. Diet restriction and temperature are the two major environmental factors to modulate aging. Diet restrictions have been demonstrated to extend lifespan through genetic mechanisms. Both homeotherms (e.g. worms/flies/fish) and poikilotherms (e.g. mice) live longer at lower body temperatures, highlighting a general role of temperature in lifespan. However, the underlying mechanisms remain elusive. Traditional views suggested that low temperatures reduce the rate of chemical reactions and thereby reduce the rate of aging through a passive thermodynamic process. Our recent work, however, challenges this view by showing that genetic programs actively promote longevity at low temperatures in C. elegans. We show that TRPA-1, a cold-sensitive TRP channel, acts as a thermo-sensor to detect temperature drop in the environment to initiate a pro-longevity genetic program. Nevertheless, our understanding of temperature regulation of lifespan is merely in its beginning. First, it remains unclear the detail of TRPA-1 mediated-lifespan. Second, other unknown genes may also regulate lifespan. Here we aim to identify new genetic network and mechanisms involved in temperature-dependent lifespan through RNAi screening in c-elegans. We will further verify the role of such involved genes and pathways in human aging and age-related diseases.With the good collaborative relationship, the laboratories in China and USA have jointly published 2 articles (cell., 2013; Cell Metabolism., 2013).