Cell：剔除肾上腺素受体基因能延长寿命
生物谷：美国科学家近日研究发现，剔除小鼠体内的某个基因能够使其活得更为长久。这为人类老化研究开辟了新的领域。相关论文发表在7月27日的《细胞》杂志上。
这个基因称为腺苷酸环化酶第五亚型(AC5)，缺乏这个基因身体就会降低对肾上腺素的敏感度，能够更好地抵抗各种压力。美国新泽西医药与牙科大学的Stephen Vatner和Junichi Sadoshima及同事曾于2003年发现，缺乏AC5的变异小鼠能够更好地抵抗心力衰竭。
在最新的研究里，他们进一步发现，AC5突变小鼠体内能更多的产生一种称作ERK2的蛋白，它能调控氧化应激(oxidative-stress，OS)反应，减轻氧化反应积累带来的损害。从而使得变异小鼠寿命比正常小鼠长30%，并且没有出现老年阶段常出现的心脏病、骨质疏松等症状。（科学网）
原始出处:
Cell, Vol 130, 247-258, 27 July 2007
Article
Type 5 Adenylyl Cyclase Disruption Increases Longevity and Protects Against Stress
Lin Yan,1,2 Dorothy E. Vatner,1 J. Patrick O'Connor,3 Andreas Ivessa,1 Hui Ge,1 Wei Chen,1 Shinichi Hirotani,1 Yoshihiro Ishikawa,1 Junichi Sadoshima,1,
and Stephen F. Vatner1,
1 Department of Cell Biology and Molecular Medicine and Cardiovascular Research Institute, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA
2 OB-GYN and Women's Health, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA
3 Orthopaedics, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA
Corresponding author
Stephen F. Vatner
vatnersf@umdnj.edu
Corresponding author
Junichi Sadoshima
sadoshju@umdnj.edu
Mammalian models of longevity are related primarily to caloric restriction and alterations in metabolism. We examined mice in which type 5 adenylyl cyclase (AC5) is knocked out (AC5 KO) and which are resistant to cardiac stress and have increased median lifespan of ∼30%. AC5 KO mice are protected from reduced bone density and susceptibility to fractures of aging. Old AC5 KO mice are also protected from aging-induced cardiomyopathy, e.g., hypertrophy, apoptosis, fibrosis, and reduced cardiac function. Using a proteomic-based approach, we demonstrate a significant activation of the Raf/MEK/ERK signaling pathway and upregulation of cell protective molecules, including superoxide dismutase. Fibroblasts isolated from AC5 KO mice exhibited ERK-dependent resistance to oxidative stress. These results suggest that AC is a fundamentally important mechanism regulating lifespan and stress resistance.
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