Lund James, Tedesco Patricia, Duke Kyle, Wang John, Kim Stuart K, Johnson Thomas E
Department of Developmental Biology, Stanford University Medical Center, Stanford, CA 94305, USA.
Curr Biol. 2002 Sep 17;12(18):1566-73. doi: 10.1016/s0960-9822(02)01146-6.
Numerous gerontogene mutants leading to dramatic life extensions have been identified in the nematode Caenorhabditis elegans over the last 20 years. Analysis of these mutants has provided a basis for understanding the mechanisms driving the aging process(es). Several distinct mechanisms including an altered rate of aging, increased resistance to stress, decreased metabolic rate, or alterations in a program causing organismic aging and death have been proposed to underlie these mutants.
Whole-genome analysis of gene expression during chronological aging of the worm provides a rich database of age-specific changes in gene expression and represents one way to distinguish among these models. Using a rigorous statistical model with multiple replicates, we find that a relatively small number of genes (only 164) show statistically significant changes in transcript levels as aging occurs (<1% of the genome). Expression of heat shock proteins decreases, while expression of certain transposases increases in older worms, and these findings are consistent with a higher mortality risk due to a failure in homeostenosis and destabilization of the genome in older animals. Finally, a specific subset of genes is coordinately altered both during chronological aging and in the transition from the reproductive form to the dauer, demonstrating a mechanistic overlap in aging between these two processes.
We have performed a whole-genome analysis of changes in gene expression during aging in C. elegans that provides a molecular description of C. elegans senescence.
在过去20年里，线虫秀丽隐杆线虫中已鉴定出许多导致寿命显著延长的老年基因（gerontogene）突变体。对这些突变体的分析为理解驱动衰老过程的机制提供了基础。已提出几种不同的机制来解释这些突变体，包括衰老速率改变、对应激的抵抗力增加、代谢率降低，或导致生物体衰老和死亡的程序改变。
对线虫按时间顺序衰老过程中的基因表达进行全基因组分析，提供了一个丰富的基因表达年龄特异性变化数据库，并且是区分这些模型的一种方法。使用具有多个重复样本的严格统计模型，我们发现随着衰老发生，相对少量的基因（仅164个）在转录水平上显示出统计学上的显著变化（占基因组不到1%）。热休克蛋白的表达降低，而某些转座酶在老龄线虫中的表达增加，并且这些发现与老龄动物因体内稳态失调和基因组不稳定导致的较高死亡风险一致。最后，一个特定的基因子集在按时间顺序衰老期间以及从生殖型向 dauer 型转变过程中均发生协调改变，这表明这两个过程在衰老机制上存在重叠。
我们对线虫衰老过程中的基因表达变化进行了全基因组分析，这为线虫衰老提供了分子描述。
