Clinical relevance of transgenic mouse models for aging research

被引:15
作者
Enns, L. C. [1 ]
Wiley, J. C. [1 ]
Ladiges, W. C. [1 ]
机构
[1] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA
来源
CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION | 2008年 / 18卷 / 01期
关键词
age-related disease; protein kinase A; catalase; mitochondria; conserved genes; invertebrate life span;
D O I
10.1615/CritRevEukarGeneExpr.v18.i1.60
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 0836 [生物工程]; 090102 [作物遗传育种]; 100705 [微生物与生化药学];
摘要
Studies on transgenic mice have shown them to be useful models for human aging- and age-related diseases. Life span end points in yeast and Caenorhabditis elegans can identify highly conserved genes that promote longevity when their functions are lost and which can readily be manipulated in the mouse. Protein kinase A is an example of a highly conserved gene that has age-delaying effects when specific subunits are suppressed or removed in the mouse, suggesting that loss of function may be a rational pharmacologic target. Gain of function is also an attractive clinical approach because expression levels of some vital genes may decrease in an age-related manner. The antioxidant enzyme catalase can delay aging when the human gene is inserted into mitochondria of mice. Other antioxidant genes are of interest in this system, both individually and in combination with catalase. A challenging aspect is to determine how to deliver catalase, as well as other gene products, into the mitochondria in the clinical setting. A number of new and exciting genes will most likely be investigated as clinical antiaging targets as the result of a forward genetic life span screening approach in invertebrates and a reverse genetic life span approach in the mouse.
引用
收藏
页码:81 / 91
页数:11
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