Tanaka Masashi
Department of Gene Therapy, Gifu International Institute of Biotechnology, Yagi Memorial Park, Mitake, Gifu 505-0116, Japan.
J Neurol. 2002 Sep;249 Suppl 2:II11-8. doi: 10.1007/s00415-002-1203-5.
We are currently sequencing the entire mitochondrial genome from 600 persons, including centenarians, patients with Parkinson's disease or diabetes, and young adults with or without obesity to search for single nucleotide polymorphisms (SNPs) associated with longevity or diseases. To test the hypothesis that centenarians are free from deleterious mitochondrial variations, we analyzed amino acid variations in cytochrome b of 64 Japanese centenarians. Although the frequencies of some variations, such as N260D and G251S, differed significantly between centenarians and patients with Parkinson's disease, the most striking feature of centenarian cytochrome b was the much greater scarceness of amino acid variations in contrast with the variety of amino acid replacements in patients with Parkinson's disease. Particular deviations from the standard amino acid sequence may be associated with increased production by mitochondria of reactive oxygen species. The absence of certain variations in centenarians and their presence in patients with Parkinson's disease indicate that these variations do not benefit long-term survival but do predispose to adult-onset diseases and that centenarians are genetically hitting the "golden mean."
我们目前正在对600人的整个线粒体基因组进行测序，其中包括百岁老人、帕金森病或糖尿病患者，以及有或没有肥胖问题的年轻人，以寻找与长寿或疾病相关的单核苷酸多态性（SNP）。为了验证百岁老人不存在有害线粒体变异这一假设，我们分析了64名日本百岁老人细胞色素b中的氨基酸变异。尽管某些变异（如N260D和G251S）的频率在百岁老人和帕金森病患者之间存在显著差异，但百岁老人细胞色素b最显著的特征是与帕金森病患者中多样的氨基酸替代相比，其氨基酸变异要稀少得多。与标准氨基酸序列的特定偏差可能与线粒体产生活性氧的增加有关。百岁老人中某些变异的缺失以及它们在帕金森病患者中的存在表明，这些变异对长期生存没有益处，反而会导致成年发病的疾病，而且百岁老人在基因上达到了“中庸之道”。
