近藤 嘉高 (コンドウ ヨシタカ)

写真a

所属

人間科学学術院 人間科学部

職名

講師(任期付)

ホームページ

https://www.waseda.jp/fhum/

学歴 【 表示 / 非表示

  • 2004年04月
    -
    2007年03月

    東京医科歯科大学   大学院博士課程   医歯学総合研究科血流制御内科学専攻  

  • 2002年04月
    -
    2004年03月

    東京医科歯科大学   大学院修士課程   医歯学総合研究科血流制御内科学専攻  

  • 1998年04月
    -
    2002年03月

    早稲田大学   教育学部   理学科 生物学専修  

学位 【 表示 / 非表示

  • 東京医科歯科大学   博士(医学)

経歴 【 表示 / 非表示

  • 2019年04月
    -
    継続中

    早稲田大学   人間科学学術院   講師(任期付)

  • 2016年04月
    -
    2019年03月

    地方独立行政法人東京都健康長寿医療センター 東京都健康長寿医療センター研究所   老化制御研究チーム 分子老化制御   研究員

  • 2014年04月
    -
    2016年03月

    東邦大学   理学部 生物分子科学科 生物医学部門   博士研究員

  • 2009年04月
    -
    2014年03月

    地方独立行政法人東京都健康長寿医療センター   東京都健康長寿医療センター研究所   研究員

  • 2008年04月
    -
    2009年03月

    東京都老人総合研究所   研究員

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所属学協会 【 表示 / 非表示

  • 2015年06月
    -
    継続中

    日本老年医学会

  • 2014年09月
    -
    継続中

    日本免疫学会

  • 2013年08月
    -
    継続中

    日本分子生物学会

  • 2008年07月
    -
    継続中

    日本未病システム学会

  • 2007年02月
    -
    継続中

    日本栄養・食糧学会

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研究分野 【 表示 / 非表示

  • 薬系衛生、生物化学

  • 食品科学

  • 分子生物学

  • 機能生物化学

  • 実験病理学

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研究キーワード 【 表示 / 非表示

  • 栄養

  • ノックアウトマウス

  • SMP30

  • GNL

全件表示 >>

論文 【 表示 / 非表示

  • Radiation-induced gastrointestinal syndrome is exacerbated in vitamin C-insufficient SMP30/GNL knockout mice.

    Reina Saga, Takahiro Uchida, Yuka Takino, Yoshitaka Kondo, Hiroaki Kobayashi, Manabu Kinoshita, Daizoh Saitoh, Akihito Ishigami, Makoto Makishima

    Nutrition (Burbank, Los Angeles County, Calif.)   81   110931 - 110931  2020年07月  [国際誌]

     概要を見る

    OBJECTIVES: Accidental exposure to high-dose radiation causes life-threatening acute radiation syndrome, features that include gastrointestinal syndrome (GIS) and hematopoietic syndrome (HS). Administration of vitamin C (VC), a free radical scavenger, has been reported to increase survival of mice in GIS and HS models. The effect of nutritional VC status on radiation injury remains unknown because, unlike humans, mice can synthesize VC. The aim of this study was to investigate the effect of VC insufficiency on acute radiation syndrome using senescence marker protein 30 (SMP30)/gluconolactonase knockout (SMP30-KO) mice. METHODS: SMP30-KO mice, which cannot synthesize VC, were given water with or without sufficient VC supplementation, and were analyzed in GIS and HS models. RESULTS: In the GIS model, in which bone marrow failure is rescued by bone marrow transplantation, VC-insufficient mice had a lower survival rate than VC-sufficient mice. The intestine of VC-insufficient GIS mice showed epithelial cell atrophy, inflammatory cell infiltration, and decreased crypt cell proliferation. We observed rapid VC oxidation after total body irradiation in the intestine of mice supplemented with VC-sufficient water. In the HS model, which was not combined with bone marrow transplantation, there was no difference in survival between VC-insufficient and -sufficient mice. CONCLUSION: The results of this study demonstrated that nutritionally sufficient VC exerts a radioprotective effect against radiation-induced GIS.

    DOI PubMed

  • Decreased ADAM17 expression in the lungs of α-Klotho reduced mouse.

    Keiko Akasaka-Manya, Hiroshi Manya, Satomi Nadanaka, Hiroshi Kitagawa, Yoshitaka Kondo, Akihito Ishigami, Tamao Endo

    Journal of biochemistry   167 ( 5 ) 483 - 493  2020年05月  [国際誌]

     概要を見る

    The deficiency of α-Klotho in mice causes phenotypes resembling human age-associated disorders at 3-4 weeks after birth and shows short lifespans of ∼2 months. One of the crucial symptoms is pulmonary emphysema, although α-Klotho is not expressed in the lungs. α-Klotho secreted from the kidneys is probably involved in the pathology of emphysema because kidney-specific knockout mice exhibit emphysematous structural changes. We examined whether any glycan changes in α-Klotho mouse lungs were observed, because α-Klotho is reported to have glycosidase activity. Here, we found the accumulation of heparan sulphate in the microsomal fraction of α-Klotho mouse lungs. Meanwhile, a disintegrin and metalloproteinase 17 (ADAM17) expression was decreased in α-Klotho mice. From these results, it is thought that the increase in heparan sulphate is due to insufficient cleavage of the core protein by ADAM17. Additionally, a reduction in α-Klotho and a decline of ADAM17 were also observed both in normal aged mice and in senescence marker protein-30 (SMP30) knockout mice, a mouse model of premature ageing. Thus, the decrease in ADAM17 is caused by the reduction in α-Klotho. These may be involved in the deterioration of lung function during ageing and may be associated with the pathology of pulmonary emphysema.

    DOI PubMed

  • Effects of rikkunshito supplementation on resistance to oxidative stress and lifespan in mice.

    Zi Wang, Toshimitsu Komatsu, Yoshihisa Ohata, Yukari Watanabe, Yiwen Yuan, Yuki Yoshii, Seongjoon Park, Ryoichi Mori, Motoyasu Satou, Yoshitaka Kondo, Isao Shimokawa, Takuya Chiba

    Geriatrics & gerontology international   20 ( 3 ) 238 - 247  2020年03月  [国内誌]

     概要を見る

    AIM: Caloric restriction (CR), which limits the caloric intake to 60-70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite-stimulating peptide, is essential for the anti-oxidative and life-extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR-like life-extending effects. METHODS: First, we evaluated the life-extending activity of RKT by examining the effect of long-term RKT administration on wild-type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR-mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high-fat diet. We then used 3-nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. RESULTS: RKT administration did not extend the lifespan of wild-type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti-oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3-nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. CONCLUSIONS: These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••-••.

    DOI PubMed

  • Acerola (Malpighia emarginata DC.) Promotes Ascorbic Acid Uptake into Human Intestinal Caco-2 Cells via Enhancing the Gene Expression of Sodium-Dependent Vitamin C Transporter 1.

    Yuka Takino, Hitoshi Aoki, Yoshitaka Kondo, Akihito Ishigami

    Journal of nutritional science and vitaminology   66 ( 4 ) 296 - 299  2020年  [国内誌]

     概要を見る

    Acerola (Malpighia emarginata DC.) is a fruit containing abundant ascorbic acid (AsA) and numerous functional phytochemicals. We previously reported that the intake of acerola juice increased the absorption of AsA in plasma of healthy Japanese subjects. The functional phytochemicals in acerola may influence the intestinal epithelial cells to increase the cellular uptake of AsA. Therefore, in this study, we compared the AsA uptake into Caco-2 cells between AsA alone and that in acerola juice at the same concentration using a human intestinal model. Caco-2 cells were incubated with 3 mM AsA and 3 mM AsA in acerola juice. Intracellular AsA contents gradually increased until 24 h upon incubation with both AsA alone and AsA in acerola juice; however, these contents when incubated with AsA in acerola juice, were significantly higher than those incubated with AsA alone at 2, 3, 4, 8, and 24 h. Furthermore, the mRNA expression level of the sodium-dependent vitamin C transporter (SVCT) 1 was significantly higher in the cells incubated with AsA in acerola juice than those incubated with AsA alone. Moreover, polyphenols such as cyanidin-3-glucoside chloride and quercetin enhanced the SVCT1 gene expression in Caco-2 cells. Collectively, these results suggest that acerola polyphenols enhances the SVCT1 gene expression in Caco-2 cells and promotes AsA uptake.

    DOI PubMed

  • Taurine Improves Lipid Metabolism and Increases Resistance to Oxidative Stress.

    Zi Wang, Yoshihisa Ohata, Yukari Watanabe, Yiwen Yuan, Yuki Yoshii, Yoshitaka Kondo, Shoko Nishizono, Takuya Chiba

    Journal of nutritional science and vitaminology   66 ( 4 ) 347 - 356  2020年  [国内誌]

     概要を見る

    Calorie restriction (CR) by 30-40% decreases morbidity of age-related diseases and prolongs the lifespan of various laboratory animal species. Taurine (2-aminoethanesulfonic acid) is an important nutrient for lipid metabolism as it conjugates bile acids. Here, we investigated how taurine supplementation induces effects similar to the CR beneficial effects. Sprague Dawley rats were fed a diet containing different taurine concentrations (0, 0.5, 1.0, 3.0, 5.0%) to analyze the effects on growth, blood, and hepatic parameters. Rats fed a 5% taurine-supplemented diet showed a significant decrease in visceral fat weight, compared with control rats. Moreover, there were significant decreases in the serum total cholesterol, hepatic cholesterol and triglyceride concentrations in the taurine-supplemented groups compared with the control group in a dose-dependent manner. These results were associated with decreased mRNA expression of fatty acid synthase, and increased mRNA expression of carnitine palmitoyltransferase 1α. C57BL/6 mice were fed a 5.0% taurine-supplemented diet, and their response to 3-nitropropionic acid-induced oxidative stress was analyzed. The rate of weight loss due to oxidative stress decreased and the survival rate significantly increased in the taurine-supplemented groups compared with the control group. Finally, cells were treated with 100 μM taurine and their resistance to UV-induced oxidative stress was analyzed. We found that the p53-Chk1 pathway was less activated in taurine-treated cells compared with control cells. Furthermore, damage to cells evaluated by oxidative stress indicators revealed a reduction in oxidative damage with taurine treatment. These findings suggest that taurine partially acts as a CR mimetic.

    DOI PubMed

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Misc 【 表示 / 非表示

  • [Molecular abnormality in aging: its contribution to clinical pathology].

    Maruyama N, Ishigami A, Kondo Y

    Rinsho byori. The Japanese journal of clinical pathology   53   728 - 734  2005年08月  [査読有り]

    PubMed

受賞 【 表示 / 非表示

  • 平成25年度 研究奨励理事長賞

    2013年06月   東京都健康長寿医療センター研究所   Smp30/Sod1ダブルノックアウトマウスを用いた非アルコール性脂肪肝(NAFLD)発症機序の解明  

    受賞者: 近藤嘉高

  • 第15回日本未病システム学会 優秀演題賞

    2008年11月   日本未病システム学会   ビタミンCの持つ抗老化作用  

    受賞者: 近藤嘉高

  • 論文賞

    2007年12月   ネスレ栄養科学会議   Senescence marker protein 30 functions as gluconolactonase in L-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy  

    受賞者: 近藤嘉高

  • 助成論文 優秀論文賞

    2005年02月   財団法人博慈会老年病研究所   Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate (DFP) in the liver  

    受賞者: 近藤嘉高

  • 若手奨励賞

    2003年06月   日本基礎老化学会  

    受賞者: 近藤嘉高

共同研究・競争的資金等の研究課題 【 表示 / 非表示

  • ビタミンC、Eの同時不足がエストロゲン欠乏マウスの皮膚に及ぼす影響

    若手研究(B)

    研究期間:

    2016年04月
    -
    2019年03月
     

    近藤 嘉高

     概要を見る

    本研究は、青壮年期の女性(エストロゲン充分)や更年期以降の女性(エストロゲン欠乏)の皮膚におけるVC不足, VE不足, 2重(同時)不足が紫外線による皮膚の黒化やシワの形成(光老化)に及ぼす影響を明らかにすることを目的とした。ビタミンCを体内で合成できないSMP30ノックアウト(KO)マウスと、エストロゲンを合成できないAromatase(Ar)-KOマウス、ヘアレスマウスを掛け合わせて、SMP30/Arダブルノックアウト(DKO)ヘアレスマウスを作出した。しかし、繁殖成績が悪く、実験に必要な匹数が得られなかった。今後は、SMP30-KOヘアレスマウスの卵巣摘出モデルに切り換えるべきである。

  • microRNAによる新しいCOPD治療を目指した気道分泌型エクソソーム解析

    研究期間:

    2017年04月
    -
    2019年03月
     

    近藤嘉高

    担当区分: 研究代表者

  • ヒト培養表皮におけるアスコルビン酸の経皮吸収および紫外線UVBによる細胞障害に対する予防、回復効果の検討

    研究期間:

    2016年04月
    -
    2017年10月
     

    近藤嘉高

    担当区分: 研究代表者

  • 動物におけるペントースリン酸副経路の同定

    若手研究(B)

    研究期間:

    2011年
    -
    2013年
     

    近藤 嘉高

    担当区分: 研究代表者

     概要を見る

    ペントースリン酸経路は、グルコース6-リン酸をグルコノラクトン6-リン酸、グルコン酸6-リン酸を経て、グリセルアルデヒド3-リン酸に代謝し、NADPHおよび核酸原料の供給を担う。細菌類では、グルコースからグルコノラクトン、グルコン酸を経て、グルコン酸6-リン酸に至る副経路が知られている。しかし、動物において副経路が存在するかどうかは不明である。本研究では、ヒトおよびマウスにおいてグルコン酸をグルコン酸6-リン酸にリン酸化するグルコン酸キナーゼの遺伝子を同定した。

  • ビタミンC合成不全マウスを用いた機能性食品の抗酸化能評価システムの開発

    若手研究(スタートアップ)

    研究期間:

    2008年
    -
    2009年
     

    近藤 嘉高

    担当区分: 研究代表者

     概要を見る

    ビタミンCを合成できないSMP30/GNLノックアウトマウスは、活性酸素種(ROS)の産生が亢進するかどうか、機能性食品の抗酸化能を評価できるかどうかを検討した。VC欠乏マウスの全身組織におけるROS産生は、顕著に増加した。また、ROS消去能をもつ水素水の投与は、VC欠乏マウスの脳におけるROS産生を抑制した。本研究から、VC欠乏マウスを用いた機能性食品の抗酸化能評価システムが確立された。

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特定課題研究 【 表示 / 非表示

  • 動物におけるペントースリン酸副経路の同定

    2020年  

     概要を見る

    Pentose phosphate pathway (PPP) produce NADPH which is utilized for fatty acid synthesis, cholesterol synthesis, and steroid biosynthesis, and redox maintenance, and ribose 5-phosphate which is necessary for synthesis of nucleic acid. It is known that alternative pathway of PPP from glucose to 6-phosphogluconate exists in bacteria, however, it remains unclear in animals. In our previous study, SMP30/gluconolactonase (GNL) hydrolyzed glucono 1,5-lactone to gluconate. To reveal a novel alternative PPP, we identified gluconokinase (GNK) gene and characterized GNK activity for phosphorylating gluconate to 6-phosphogluconate. To reveal tissue distribution of GNK in mouse, we measured gene expression levels of GNK, and compared with those of SMP30/GNL, glucose 6-phosphate dehydrogenase (G6PD), and 6-phosphogluconolactonase (6PGL). Six C57BL/6J male mice were dissected at 8 weeks of age, and 20 kinds of tissues were collected. Gene expression levels of GNK, SMP30/GNL, G6PD, and 6PGL were quantified by using real-time PCR. GNK, SMP30/GNL, G6PD and 6PGL genes were ubiquitously expressed in almost all tissues. GNK gene was highly expressed in liver, kidney, duodenum, and brown fat. Gene expression of SMP30/GNL was most abundant in liver, subsequently in kidney, duodenum, and adrenal gland. G6PD gene was highly expressed in epididymal fat, brown fat, adrenal gland, and testis. 6PGL gene showed higher expression in brown fat and testis. Overall, tissue distribution of GNK gene expression showed similarity to that of SMP30/GNL, which is distinct from those of G6PD and 6PGL. These results suggest that GNK and SMP30/GNL could cooperatively functions in alternative PPP.

  • 動物におけるペントースリン酸副経路の同定

    2020年  

     概要を見る

    Pentose phosphate pathway (PPP) produce NADPH which is utilized for fatty acid synthesis, cholesterol synthesis, and steroid biosynthesis, and redox maintenance, and ribose 5-phosphate which is necessary for synthesis of nucleic acid. It is known that alternative pathway of PPP from glucose to 6-phosphogluconate exists in bacteria, however, it remains unclear in animals. In our previous study, SMP30/gluconolactonase (GNL) hydrolyzed glucono 1,5-lactone to gluconate, and gluconokinase (GNK) catalyzed phosphorylation of gluconate to 6-phosphogluconate in human and mouse. To reveal tissue distribution of GNK in mouse, we measured gene expression levels of GNK, and compared with those of SMP30/GNL, glucose 6-phosphate dehydrogenase (G6PD), and 6-phosphogluconolactonase (6PGL).Six C57BL/6J male mice were dissected at 8 weeks of age, and 20 kinds of tissues were collected. Gene expression levels of GNK, SMP30/GNL, G6PD, and 6PGL were quantified by using real-time PCR. GNK, SMP30/GNL, G6PD and 6PGL genes were ubiquitously expressed in almost all tissues. GNK gene was highly expressed in liver, kidney, duodenum, and brown fat. Gene expression of SMP30/GNL was most abundant in liver, subsequently in kidney, duodenum, and adrenal gland. G6PD gene was highly expressed in epididymal fat, brown fat, adrenal gland, and testis. 6PGL gene showed higher expression in brown fat and testis.Overall, tissue distribution of GNK gene expression showed similarity to that of SMP30/GNL, which is distinct from those of G6PD and 6PGL. These results suggest that GNK and SMP30/GNL could cooperatively functions in alternative PPP.

  • 新規ペントースリン酸経路で働くグルコン酸キナーゼのマウスにおける発現解析

    2020年  

     概要を見る

    Pentose phosphate pathway (PPP) produce NADPH which is utilized for fatty acid synthesis, cholesterol synthesis, and steroid biosynthesis, and redox maintenance, and ribose 5-phosphate which is necessary for synthesis of nucleic acid. It is known that alternative pathway of PPP from glucose to 6-phosphogluconate exists in bacteria, however, it remains unclear in animals. In our previous study, SMP30/gluconolactonase (GNL) hydrolyzed glucono 1,5-lactone to gluconate, and gluconokinase (GNK) catalyzed phosphorylation of gluconate to 6-phosphogluconate in human and mouse. To reveal tissue distribution of GNK in mouse, we measured gene expression levels of GNK, and compared with those of SMP30/GNL, glucose 6-phosphate dehydrogenase (G6PD), and 6-phosphogluconolactonase (6PGL).Six C57BL/6J male mice were dissected at 8 weeks of age, and 20 kinds of tissues were collected. Gene expression levels of GNK, SMP30/GNL, G6PD, and 6PGL were quantified by using real-time PCR. GNK, SMP30/GNL, G6PD and 6PGL genes were ubiquitously expressed in almost all tissues. GNK gene was highly expressed in liver, kidney, duodenum, and brown fat. Gene expression of SMP30/GNL was most abundant in liver, subsequently in kidney, duodenum, and adrenal gland. G6PD gene was highly expressed in epididymal fat, brown fat, adrenal gland, and testis. 6PGL gene showed higher expression in brown fat and testis.Overall, tissue distribution of GNK gene expression showed similarity to that of SMP30/GNL, which is distinct from those of G6PD and 6PGL. These results suggest that GNK and SMP30/GNL could cooperatively functions in alternative PPP.

  • 動物におけるペストースリン酸副経路の同定

    2019年  

     概要を見る

    Pentose phosphate pathway (PPP) is a metabolic pathway parallel to glycolysis, which generates nicotinamide adenine dinucleotide phosphate (NADPH) for reductive biosynthesis reactions and pentoses as well as such as ribose 5-phosphate, a precursor for the synthesis of nucleotides. 6-phosphogluconate is an intermediate in PPP which metabolize glucose 6-phosphate to glyceraldehyde 3-phosphate. In bacteria, it is known that alternative pathway of PPP metabolize glucose to 6-phosphogluconate. However, it has not been reported in human and mouse. To reveal a novel alternative PPP, we identified gluconokinase (GNK) gene and characterized GNK activity for phosphorylating gluconte to 6-phosphogluconate.By NCBI-BLAST search, amino acid sequence of bacterial GNK in Pseudomonas putida KT2440 showed high homology with those of possible GNK gene (NM_001001551 and NM_198004) in human and mouse, respectively. We cloned cDNA of possible GNK gene from liver in human and mouse. Recombinant 6xHis-tagged proteins were purified from bacterial soluble fraction by using Ni-NTA agarose and DEAE-Sephacel column. GNK activity in reaction mixture containng gluconate, ATP, MgCl2, and recombinant GNK protein was measured by monitoring A340 of NADPH generated in coupled with resulting 6-phosphogluconate, NADP+, and 6-phosphogluconate dehydrogenase. Human and mouse recombinat proteins showed GNK activity in dose-dependent manner, respectively. Furthermore, GNK activity was detected in mouse liver extract.In this study, we identified GNK gene in human and mouse, suggesting that alternative PPP could exists in human and mouse.

  • 動物におけるペントースリン酸副経路の同定

    2019年  

     概要を見る

    Pentose phosphate pathway (PPP) is a metabolic pathway parallel to glycolysis, which generates nicotinamide adenine dinucleotide phosphate (NADPH) for reductive biosynthesis reactions and pentoses as well as such as ribose 5-phosphate, a precursor for the synthesis of nucleotides. 6-phosphogluconate is an intermediate in PPP which metabolize glucose 6-phosphate to glyceraldehyde 3-phosphate. In bacteria, it is known that alternative pathway of PPP metabolize glucose to 6-phosphogluconate. However, it has not been reported in human and mouse. To reveal a novel alternative PPP, we identified gluconokinase (GNK) gene and characterized GNK activity for phosphorylating gluconte to 6-phosphogluconate.By NCBI-BLAST search, amino acid sequence of bacterial GNK in Pseudomonas putida KT2440 showed high homology with those of possible GNK gene (NM_001001551 and NM_198004) in human and mouse, respectively. We cloned cDNA of possible GNK gene from liver in human and mouse. Recombinant 6xHis-tagged proteins were purified from bacterial soluble fraction by using Ni-NTA agarose and DEAE-Sephacel column. GNK activity in reaction mixture containng gluconate, ATP, MgCl2, and recombinant GNK protein was measured by monitoring A340 of NADPH generated in coupled with resulting 6-phosphogluconate, NADP+, and 6-phosphogluconate dehydrogenase. Human and mouse recombinat proteins showed GNK activity in dose-dependent manner, respectively. Furthermore, GNK activity was detected in mouse liver extract.In this study, we identified GNK gene in human and mouse, suggesting that alternative PPP could exists in human and mouse.

 

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委員歴 【 表示 / 非表示

  • 2017年04月
    -
    継続中

    日本基礎老化学会  評議員

  • 2012年04月
    -
    2014年03月

    日本基礎老化学会  評議員・編集委員