Murakami S, Johnson T E
Institute for Behavioral Genetics, University of Colorado at Boulder 80309-0447, USA.
Curr Biol. 1998 Sep 24;8(19):1091-4. doi: 10.1016/s0960-9822(98)70448-8.
The nematode Caenorhabditis elegans is widely used to study aging, development, behavior and other basic metazoan processes [1-3]. The only mutants directly identified on the basis of their extended longevity in any metazoan have been isolated in C. elegans [4,5]. All life-extension mutants (Age mutants) previously identified in C. elegans result from hypo-morphic or nullo-morphic mutations. We have identified a new class of gerontogene (a gene whose alteration causes life extension) that increases life span when overexpressed. The first gene in this class has been designated tyrosine kinase receptor-1 (tkr-1); it encodes a putative receptor tyrosine kinase. Overexpression of tkr-1 in transgenics increases longevity 40-100% (average 65%), confers increased resistance to heat and ultraviolet (UV) irradiation in transgenic nematodes, and does not alter development or fertility. Unlike previously identified gerontogenes, tkr-1 positively modulates stress resistance and longevity. These results further support the positive relationship between increased stress resistance and increased longevity seen in all previously studied longevity mutants. This transgenic system is an effective means for identifying overexpression gerontogenes.
线虫秀丽隐杆线虫被广泛用于研究衰老、发育、行为及其他后生动物的基本过程[1 - 3]。在任何后生动物中，唯一基于延长寿命直接鉴定出的突变体是在秀丽隐杆线虫中分离得到的[4,5]。先前在秀丽隐杆线虫中鉴定出的所有寿命延长突变体（衰老突变体）均源于亚效等位或无效等位突变。我们鉴定出了一类新的衰老基因（其改变会导致寿命延长的基因），该基因过表达时会延长寿命。这类基因中的第一个已被命名为酪氨酸激酶受体 - 1（tkr - 1）；它编码一种假定的受体酪氨酸激酶。tkr - 1在转基因动物中的过表达使寿命延长40 - 100%（平均65%），赋予转基因线虫对热和紫外线（UV）照射更强的抗性，且不改变发育或生育能力。与先前鉴定出的衰老基因不同，tkr - 1正向调节应激抗性和寿命。这些结果进一步支持了在所有先前研究的长寿突变体中观察到的应激抗性增强与寿命延长之间的正相关关系。这个转基因系统是鉴定过表达衰老基因的有效手段。
