MITOCHONDRIAL GENOTYPE ASSOCIATED WITH LONGEVITY

与长寿相关的线粒体基因型

• 批准号: 10832009
• 负责人: TANAKA Masashi
• 金额: $ 2.11万
• 依托单位: Institute of Applied Biochemistry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10832009/
• 关键词: mitochondria! DNA; longevity; single nucleotide polymorphism; mutagenesis; diabetes mellitus; cardiac infarction; arteriosclerosis; Parkinson's disease; 変異発生

Mitochondria are not only the major site of ATP production in cells but also an important source of reactive oxygen species (ROS) under certain pathological conditions. Because mitochondrial DNA (mtDNA) in the mitochondrial matrix is exposed to ROS that leak from the respiratory chain, this extranuclear genome is prone to mutations. Therefore, the mitochondrial genome is a rich source of single nucleotide polymorphisms (SNPs), and the functional significance of SNPs in the mitochondrial genome is comparable to that of SNPs in the entire nuclear genome. To demonstrate the contribution of mitochondrial SNPs to the susceptibility to adult-onset diseases, we analysed the mtDNA from Japanese centenarians, and identified a longevity-associated mitochondrial genotype, Mt5178A. Because this genotype was demonstrated to suppress the occurrence of mtDNA mutations in the oocytes, it also would seem to decelerate the accumulation of mtDNA mutations in the somatic cells with increasing age. This genotype is likely to confer resistance to adult-onset diseases by suppressing obesity and atherosclerosis.

线粒体不仅是细胞中产生ATP的主要部位，而且在一定病理条件下也是活性氧（ROS）的重要来源。由于线粒体基质中的线粒体DNA （mtDNA）暴露于从呼吸链泄漏的活性氧中，这种核外基因组容易发生突变。因此，线粒体基因组是单核苷酸多态性（snp）的丰富来源，线粒体基因组中snp的功能意义与整个核基因组中snp的功能意义相当。为了证明线粒体snp对成人发病疾病易感性的贡献，我们分析了来自日本百岁老人的mtDNA，并确定了长寿相关的线粒体基因型Mt5178A。由于该基因型被证明可以抑制卵母细胞中mtDNA突变的发生，它似乎也可以随着年龄的增长而减缓体细胞中mtDNA突变的积累。这种基因型可能通过抑制肥胖和动脉粥样硬化而赋予对成人发病疾病的抵抗力。

项目成果

Gong J-S, Tanaka M et al.: "Mitochondrial genotype frequent in centenarians predisposes resistance to adult-onset diseases"J.Clin.Biochem.Nutr.. 24. 105-111 (1998)

Kong J-S、Tanaka M 等：“百岁老人中常见的线粒体基因型易对成人发病的疾病产生抵抗力”J.Clin.Biochem.Nutr.. 24. 105-111 (1998)

田中雅嗣: "ミトコンドリア心筋症 循環機能検査ハンドック(北畠顕, 小川聡, 永井良三, 堀 正二編)"中山書店. 545-548 (1998)

田中正继：《线粒体心肌病循环功能检查手册》（北畠彰、小川聪、永井良三、堀正二编）》中山书店545-548（1998）。

米由誠, 田中雅嗣: "ミトコンドリアと老化 新老年学〔第2版〕(折茂 肇, 井藤英喜, 冷水 豊, 江藤文夫, 袖井孝子, 大内尉義, 福地義之助, 後藤佐多良, 藤田美明, 柴田博編)"東京大学出版会. 80-84 (1999)

Yusei Yone、Masatsugu Tanaka：“线粒体与衰老新老年学[第二版]”（Hajime Orimo、Hideki Ito、Yutaka Hizumi、Fumio Eto、Takako Sodei、Takayoshi Ouchi、Yoshinosuke Fukuchi、Satara Goto、Mi Fujita Akira、Hiroshi Shibata（编辑） .），东京大学出版社 80-84（1999）。

Shimokata H, Yamada Y, Nakagawa M, Okubo R, Saido T, Funakoshi A, Miyasaka K, Ohta S, Tsujimoto G, Tanaka M, Ando F, Niino N.: "Distribution fo geriatric disease related genotypes in the National Institute for Longevity Sciences, Longitudinal Study of Agi

Shimokata H、Yamada Y、Nakakawa M、Okubo R、Saido T、Funakoshi A、Miyasaka K、Ohta S、Tsujimoto G、Tanaka M、Ando F、Niino N.：“国家长寿研究所老年疾病相关基因型的分布

Kita K.,Tsuda J.,Kato T.,Okamoto K.,Yanase H.and Tanaka M.: "Evidence of horizontal transfer of the EcoO109I restriction-modification gene to Escherichia coli chromosomal DNA"J.Bacteriol.. 181. 6822-6827 (1999)

Kita K.、Tsuda J.、Kato T.、Okamoto K.、Yanase H. 和 Tanaka M.：“EcoO109I 限制性修饰基因水平转移至大肠杆菌染色体 DNA 的证据”J.Bacteriol.. 181. 6822