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MITOCHONDRIAL GENOTYPE ASSOCIATED WITH LONGEVITY

Research Project

Project/Area Number 10832009
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 老化(加齢)
Research InstitutionInstitute of Applied Biochemistry

Principal Investigator

TANAKA Masashi  INSTITUTE OF APPLIED BIOCHEMISTRY DEPARTMENT OF GENE THERAPY DIRECTOR, 研究部長 (60155166)

Co-Investigator(Kenkyū-buntansha) YAGI Kunio  INSTITUTE OF APPLIED BIOCHEMISTRY, PRESIDENT, 所長 (00022749)
YONEDA Makoto  FYKUI MEDICAL UNIVERSITY DEPARTMENTOF MEDICINE, ASSISTANT PROFESSOR, 第二内科, 助手 (70270551)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsmitochondria! DNA / longevity / single nucleotide polymorphism / mutagenesis / diabetes mellitus / cardiac infarction / arteriosclerosis / Parkinson's disease / 変異発生
Research Abstract

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.

Report

(3 results)
  • 2001 Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Tanaka M et al.: "Mitochondrial genotype associated with longevity"Lancet, 1998. 351. 185-186 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhang J, Tanaka M et al.: "Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causin2 encephalomyopathy"Biochem.Mol.Biol.Int.. 46. 71-79 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura J, Tanaka M et al.: "An IDDM patient who complained of chest oppression with ischemic changes on ECG in insulin-induced hypoglycemia"Diabetes Res.Clin.Pract.. 39. 31-37 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsumori A, Tanaka M et al.: "Hepatitis C virus infection and heart diseases : a multicenter study in Japan"Jpn.Circ.J.. 62. 31-37 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hattori N, Tanaka M et al.: "Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex and susceotibilitv to Parkinson disease"Genomics. 49. 52-58 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Borgeld H-J W, Tanaka M et al.: "Appropriately spaced nuclear localizing signals are necessary for efficient nuclear import of non-nuclear proteins"Biochem.Biophys.Res.Commun.. 256. 278-283 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田中雅嗣: "ミトコンドリアDNAと長寿"臨床検査. 42. 1571-1575 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田中雅嗣: "ミトコンドリアと老化"実験医学. 16. 2293-2299 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田中雅嗣: "ヒトの老化とミトコンドリアDNA"生物の科学遺伝. 52. 32-37 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田中雅嗣: "神経系の老化とミトコンドリア"神経進歩. 42. 719-726 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田中雅嗣: "ミトコンドリアDNA多型と長寿"臨床化学. 27. 192-201 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田中雅嗣: "ミトコンドリアと活性酸素"Clinical Neuroscience. 17. 348-349 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 田中雅嗣: "長寿あるいは成人発症性疾患に関連するミトコンドリア遺伝子型 心筋の構造と代謝-1997-Vol.20"六法出版社. 235-240 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fuku N, Oshida Y, Takeyasu T, Guo L-J, Kurata M, Yamada Y, Sato Y, Tanaka M.: "Mitochondrial ATPase subunit 6 and cytochrome b gene polymorphisms in young obese adults"Biochem Biophys Res Commun. 290. 1199-1205 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsunaga H, Tanaka Y, Tanaka M, Gong JS, Zhang J, Nomiyama T, Ogawa O, Ogihara T, Yamada Y, Yagi K, Kawamori R.: "Antiatherogenic mitochondrial genotype I npatients with type 2 diabetes"Diabetes Care. 24. 500-503 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mizutani J, Chiba T, Tanaka M, Higuchi K, Mori M.: "Unique mutations in mitochondrial DNA of senescence accelerated mouse (SAM) strains"J Hered. 92. 352-355 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sahashi K, Yoneda M, Ohno K, Tanaka M, Ibi T.: "Functional characterisation of mitochondrial tRNA (Tyr) mutation (5877->GA) associated with familial chronic progressive external ophthalmoplegia"J Med Genet. 38. 703-705 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka M.: "Mitochondrial DNA Polymorphisms and Aging"Environ Mutagen Res. 23. 197-205 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Terasaki F, Tanaka M, Kawamura K. Kanzaki Y, Okabe M, Hayashi T, Shimomura H, Ito T, Suwa M, Gong JS, Zhang J, Kitaura Y.: "A case of cardiomyopathy showing progression from the hypertrophic to the dilated form : association of Mt8348A->G mutation in the mitochondrial tRNA (Lys)gene with severe ultrastructural alterations of mitochondria in cardiomyocytes"Jpn Circ J. 65. 691-694 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Umetsu K, Tanaka M, Yuasa I, Saitou N, Takeyasu T, Fuku N, Nito E, Ago K, Nakayashiki n, Miyoshi A, Kashimura S, Watanabe G, Osawa M.: "Multiplex length polymorphism analysis for rapid detection of human mitochondrial DNA variations amplified product"Electrophoresis. 22. 3533-3538 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada Y, ichihara S, Izawa H, Tanaka M, Yokota M.: "Association of a G994->T (Val279->Phe) polymorphism of the plasma platelet-activating factor acetylhydrolase gene with myocardial damage in Japanese patients with nonfamilial hypertrophic cardiomyopathy"J Hum Genet. 46. 436-441 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada Y, ichihara S, Izawa H, Tanaka M, Yokota M.: "Association of the 509C->T polymorphism, alone or in combination with the T869>C polymorphism, of the transforming growth factor beta1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women"J Mol Med. 79. 149-156 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura J, Uchigata Y, Gong J-S, Zhang J, Iwamoto Y, Yagi K, Tanaka M.: "Mitochondrial genotype Mt5178C is associated with diabetic nephropahty in Japanese type 1 diabetic patients"Diabetes Mellitus : Recent Advances for the 21st Century, M. Shichiri, S. Shinn, N. Hotta Edutors. Elsevier Science : Tokyo. 271-274 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 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 Agint (NILS LSA)"J Epidemiol. 10. S46-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shin WS, Tanaka M, Suzuki J, Hemmi C, Toyo-oka T.: "A novel homoplasmic mutation in mtDNA with a single evolutionary origin as a risk factor for cardiomyopathy"Am J Hum Genet. 67. 1617-1620 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka M, Gong J, Zhang J, Yamada Y, Borgeld H, Yagi K.: "Mitochondrial Genotype associated with longevity and its Mech inhibitory effect on mutagenesis"Ageing Dev.. 116. 65-76 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Borgeld HJ, Naruse K, Nishikawa S, Zhang J, Kikuchi A, Furukawa K, Yagi K, Tanaka M.: "Appropriately spaced nuclear localizing singnals are necessary for effcient nuclear import of nunnuclear proteins"Biochem Biophys Res Commun. 256. 27883 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kita K, Tsuda J, Kato T, Okamoto K, Yanase H, Tanaka M.: "Evidence of horizontal transfer of the EcoO109I restriction modification gene to escherichia coli chromosomal DNA"J Bacteriol. 181. 6822-6827 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gong J-S, Zhang J, Yoneda M, Sahashi K, Miyajima H, Yamauchi K, Tanaka M.: "Mitochondrial genotype frequent in centenarians predisposes resistance to adult-onset diseases"J Clin. Biochem. Nutr. 26. 46-47 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y.: "Genotype in the 24-kDa subunit gene (NDUFV2) fo mitochondrial complex I and susceptibility to Parkinson disease"Genomics. 49. 52-58 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kishi T, Kawahara H, Tanaka T, Kaneko Y, Tsuji T, Kawaguchi H, Nishio Y, Hata S, Kawamura T, Sakamoto K, Tanaka M, Satoh W.: "Superior mesenteric artery syndrome complicating mitochondrial encephalopathy"J pediatr Gastroenterol Nutr. 26. 46-47 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matumori A, Ohashi N, Hasegawa K, Sasayama S, Eto T, Imaizumi T, Izumi T, Kawamura K, Kawana M, Kimura A, Kitabatake A, Matsuzaki M, Nagai R, Tanaka H, Hiroe M, Hori M, Inoko H, Seko Y, Sekiguchi M, Shimotohno K, Sugihita Y, Takeda N, Takihara K, Tanaka M: "hepatitis C virus infection and heart diseases : a multicenter study in Japan"Jpn. Circ. J. 62. 389-391 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura J, Uchigata Y, Sato A, Matsunaga R, Fujito T, Borgeld HJ, Tanaka M, Babazono T, Takahashi C, Iwamoto Y.: "An IDDM patient who complained of chest oppression with ischemic changes on ECG in insulin-induced hypoglycemia"Diagetes. Res. Clin. Pract.. 39. 31-37 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K.: "Mitochondrial genotype associated with longevity"Lancet. 351. 185-186 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhang J, Yoneda M, Naruse K, Borgeld HJ, Gong JS, Obata S, Tanaka M, Yagi K.: "Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy"Biochem Mol Bio Int. 46. 71-79 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Borgeld H.-J.W.,Naruse K.,Nishikawa S.-i.,Zh ang J.,Kikuchi A.,Furukawa K.,Yagi K.and Tanaka M.: "Appropriately spaced nuclear localizing signals are necessary for efficient nuclear import of non-nuclear proteins"Biochem.Biophys.Res.Commun.. 256. 278-283 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 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)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田中雅嗣: "長寿に関連するミトコンドリア遺伝子型と成人発症性疾患への影響"最新医学. 54. 1122-1128 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリアと老化"脳と神経. 51. 589-599 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリアと活性酸素"Clinical Neuroscience. 17. 348-349 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリアと老化"BIO Clinica. 15. 214-219 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka M et al: "Mitochondrial genotype associated with longevity." Lancet,1998. 351. 185-186 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 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)

    • Related Report
      1998 Annual Research Report
  • [Publications] Zhang J,Tanaka M et al: "Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy" Biochem.Mol.Biol.Int.46. 71-79 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miura J,Tanaka M et al: "An IDDM patient who complained of chest oppression with ischemic changes on ECG in insulin-induced hypoglycemia" Diabetes Res.Clin.Pract.39. 31-37 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsumori A,Tanaka M et al: "Hepatitis C virus infection and heart diseases:a multicenter study in Japan" Jpn.Circ.J.62. 389-391 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hattori N,Tanaka M et al: "Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and susceptibility to Parkinson disease" Genomics. 49. 52-58 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Borgeld H-J W,Tanaka M et al: "Appropriately spaced nuclear localizing signals are necessary for efficient nuclear import of non-nuclear proteins" Biochem.Biophys.Res.Commun.in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリアDNAと長寿" 臨床検査. 42. 1571-1575, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリアと老化" 実験医学. 16. 2293-2299 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣: "ヒトの老化とミトコンドリアDNA" 生物の科学 遺伝. 52. 32-37 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣: "神経系の老化とミトコンドリア" 神経進歩. 42. 719-726 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリアDNA多型と長寿" 臨床化学. 27. 192-201 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリアと活性酸素" Clinical Neuroscience. 17. 348-349 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣: "ミトコンドリア心筋症 循環機能検査ハンドブック(北畠 顕,小川 聡,永井良三,堀 正二編)" 中山書店, 545-548 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中雅嗣ら: "長寿あるいは成人発症性疾患に関連するミトコンドリア遺伝子型 心筋の構造と代謝-1997-Vol.20" 六法出版社, 235-240 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 米田 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)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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