Effects of simultaneous deficiency of vitamins C and E on memory, learning behavior, lipid metabolism, aging and age-associated disease

• Project/Area Number: 15H04505
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Food science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: Ishigami Akihito 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), 東京都健康長寿医療センター研究所, 研究部長 (50270658)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 老化 / 食品

Outline of Final Research Achievements

We established SMP30/αTTP double knockout mice as a novel double-deficient model for both vitamin C and vitamin E. SMP30/αTTP double knockout mice showed impaired cue and context-dependent fear memory if both vitamin C and vitamin E were deficient. Moreover, simultaneous deficiency of vitamin C and E revealed that it affects lipid metabolism in the liver.

Research Products

• [Journal Article] Acerola (Malpighia emarginata DC.) Juice Intake Suppresses UVB-Induced Skin Pigmentation in SMP30/GNL Knockout Hairless Mice (2017)
  • Author(s): Sato Yasunori、Uchida Eriko、Aoki Hitoshi、Hanamura Takayuki、Nagamine Kenichi、Kato Hisanori、Koizumi Takeshi、Ishigami Akihito
  • Journal Title: PLOS ONE Volume: 12 Pages: 0170438-0170438
  • DOI: 10.1371/journal.pone.0170438
  • Peer Reviewed / Open Access
• [Journal Article] Age-related changes of vitamin E: α-tocopherol levels in plasma and various tissues of mice and hepatic α-tocopherol transfer protein (2017)
  • Author(s): Takahashi, K., Takisawa, S., Shimokado, K., Kono, N., Arai, H., Ishigami, A.
  • Journal Title: European Journal of Nutrition Volume: 印刷中 Pages: 1317-1327
  • DOI: 10.1007/s00394-016-1182-4
  • Peer Reviewed
• [Journal Article] Bone degeneration and its recovery in SMP30/GNL-knockout mice (2017)
  • Author(s): Nishijima Kazutoshi、Ohno T.、Amano A.、Kishimoto Y.、Kondo Y.、Ishigami A.、Tanaka S.
  • Journal Title: The journal of nutrition, health & aging Volume: 21 Pages: 573-578
  • DOI: 10.1007/s12603-016-0841-8
  • NAID: 130007537588
  • Peer Reviewed
• [Journal Article] Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice (2017)
  • Author(s): Suzuki Yohei、Sato Tadashi、Sugimoto Masataka、Baskoro Hario、Karasutani Keiko、Mitsui Aki、Nurwidya Fariz、Arano Naoko、Kodama Yuzo、Hirano Shin-ichi、Ishigami Akihito、Seyama Kuniaki、Takahashi Kazuhisa
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 492 Pages: 74-81
  • DOI: 10.1016/j.bbrc.2017.08.035
  • Peer Reviewed
• [Journal Article] Antioxidant nutrients in plasma of Japanese patients with chronic obstructive pulmonary disease, asthma-COPD overlap syndrome and bronchial asthma (2017)
  • Author(s): Kodama Y, Kishimoto Y, Muramatsu Y, Tatebe J, Yamamoto Y, Hirota N, Itoigawa Y, Atsuta R, Koike K, Sato T, Aizawa K, Takahashi K, Morita T, Homma S, Seyama K, Ishigami A.
  • Journal Title: The Clinical Respiratory Journal Volume: ー Pages: 1-10
  • DOI: 10.1111/crj.12436
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Involvement of senescence marker protein-30 in glucose metabolism disorder and nonalchoholic fatty liver disease. (2016)
  • Author(s): Kondo Y, Ishigami A.
  • Journal Title: Geriatr Gerontol Int. Volume: Suppl 1 Pages: 4-16
  • DOI: 10.1111/ggi.12722
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Attenuated phagocytosis of secondary necrotic neutrophils by macrophages in aged and SMP30 knockout mice. (2016)
  • Author(s): 1.Takahashi, R., Totsuka, S., Ishigami, A., Kobayashi Y., and Nagata, K.
  • Journal Title: Geriatr Gerontol Int. Volume: 17 Pages: 1111-1111
  • DOI: 10.1111/ggi.12436
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Senescence marker protein-30 deficiency impairs angiogenesis under ischemia (2016)
  • Author(s): Yamauchi H, Miura S, Owada T, Saitoh S, Machii H, Yamada S, Ishigami A, Takeishi Y.
  • Journal Title: Free Radical Biology and Medicine Volume: 94 Pages: 66-73
  • DOI: 10.1016/j.freeradbiomed.2016.02.020
  • Peer Reviewed / Open Access
• [Journal Article] Skewing of peritoneal resident macrophages toward M1-like is involved in enhancement of inflammatory responses induced by secondary necrotic neutrophils in aged mice. (2016)
  • Author(s): Takahashi R, Ishigami A, Kobayashi Y, Nagata K.
  • Journal Title: Cellular Immunol. Volume: 304-305 Pages: 44-48
  • DOI: 10.1016/j.cellimm.2016.03.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion (2016)
  • Author(s): Kadowaki S, Shishido T, Sasaki T, Sugai T, Narumi T, Honda Y, Otaki Y, Kinoshita D, Takahashi T, Nishiyama S, Takahashi H, Arimoto T, Miyamoto T, Watanabe T, Ishigami A, Takeishi Y, Kubota I.
  • Journal Title: International Journal of Molecular Sciences Volume: 17 Pages: 54-54
  • DOI: 10.3390/ijms17040542
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vitamin C impacts anxiety-like behavior and stress-induced anorexia relative to social environment in SMP30/GNL knockout mice. (2016)
  • Author(s): Koizumi M, Kondo Y, Isaka A, Ishigami A, Suzuki E.
  • Journal Title: Nutrition Research Volume: 36 Pages: 1379-1391
  • DOI: 10.1016/j.nutres.2016.11.006
  • NAID: 130007537603
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pharmacological and genetic reappraisals of protease and oxidative stress pathways in a mouse model of obstructive lung diseases (2016)
  • Author(s): Shuto T, Kamei S, Nohara H, Fujikawa H, Tasaki Y, Sugahara T, Ono T, Matsumoto C, Sakaguchi Y, Maruta K, Nakashima R, Kawakami T, Suico MA, Kondo Y, Ishigami A, Takeo T, Tanaka KI, Watanabe H, Nakagata N, Uchimura K, Kitamura K, Li JD, Kai H.
  • Journal Title: Scientific Reports Volume: 6 Pages: 39305-39305
  • DOI: 10.1038/srep39305
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes. (2015)
  • Author(s): Ohta, Mitsuhiro; Fujinami, Aya; Kobayashi, Norihiro; Amano, Akiko; Ishigami, Akihito; Tokuda, Harukuni; Suzuki, Nobutaka; Ito, Fumitake; Mori, Taisuke; Sawada, Morio;
  • Journal Title: Nutr. Res. Volume: 35(7) Pages: 618-625
  • DOI: 10.1016/j.nutres.2015.05.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to maintenance of immune cells in vitamin C-deficient SMP30 knockout mice. (2015)
  • Author(s): Uchio, R., Hirose, Y., Murosaki, S., Yamamoto, Y., Ishigami, A.
  • Journal Title: Br. J. Nutr. Volume: 113 Pages: 603-609
  • DOI: 10.1017/s0007114514003857
  • Peer Reviewed
• [Journal Article] Senescence marker protein-30/gluconolactonase deficiency exacerbates diabetic nephropathy through tubular injury in a mouse model of type 1 diabetes. (2015)
  • Author(s): Okada, H., Senmaru, T., Fukui, M., Kondo, Y., Ishigami, A., Maruyama, N., Obayashi, H., Yamazaki, M., Nakamura, N., Hasegawa, G.
  • Journal Title: J. Diabetes. Invest. Volume: 6 Pages: 35-43
  • DOI: 10.1111/jdi.12252
  • Peer Reviewed
• [Journal Article] Anti-inflammatory activity of SMP30 modulates NF-κB through protein tyrosine kinase/phosphatase balance. (2015)
  • Author(s): Jung, K.J., Lee, E.K., Kim, S.J., Song, C.W., Maruyama, N., Ishigami, A., Kim, N.D., Im, D.S,, Yu, B.P., Chung, H.Y.
  • Journal Title: J. Mol. Med. Volume: 6 Pages: 35-43
  • DOI: 10.1007/s00109-014-1219-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Age-associated decrease of senescence marker protein-30/gluconolactonase in individual mouse liver cells: Immunohistochemistry and immunofluorescence. (2015)
  • Author(s): Ishigami, A., Masutomi, H., Handa, S., Maruyama, N.
  • Journal Title: Geriatr. Gerontol. Int. Volume: 15 Pages: 804-810
  • DOI: 10.1111/ggi.12347
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Vitamin C deficiencr leads to skeletal muscle atrophy. (2017)
  • Author(s): Ishigami, A.
  • Organizer: 2017 Aging Seminar between Korea and Japan
  • Int'l Joint Research / Invited
• [Presentation] Vitamin C Deficiency Leads to Skeletal Muscle Atrophy and Muscle Fiber Transformation (2017)
  • Author(s): Kondo Y, Takisawa S, Noda Y, Machida S, Aigaki T, Ishigami A.
  • Organizer: IAGG 2017
  • Int'l Joint Research
• [Presentation] Vitamin C deficiency in skeletal muscle switches muscle fiber types from slow to fast (2017)
  • Author(s): Kondo Y, Takisawa S, Noda Y, Machida S, Aigaki T, Ishigami A.
  • Organizer: ICFSR 2017
  • Int'l Joint Research
• [Presentation] SMP30/SOD1-double knockout mice manifest increased oxidative stress, hepatic steatosis, and premature death (2017)
  • Author(s): Ishigami A, Kasahara Y, Kondo Y.
  • Organizer: Asian Society of Aging Research Symposium 2017
  • Int'l Joint Research
• [Presentation] 抗酸化ビタミンC, Eによるアンチエイジング (2017)
  • Author(s): 石神昭人
  • Organizer: 日本ビタミン学会第69回大会
  • Invited
• [Presentation] ヒト培養表皮を用いた紫外線照射によるビタミンCの細胞傷害抑制効果 (2016)
  • Author(s): 河島早紀、永田喜三郎、佐藤安訓、吉田雅幸、石神昭人
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜, 横浜市, 神奈川県
  • Year and Date: 2016-11-30
• [Presentation] 経皮吸収したビタミンCによる紫外線（UVB）細胞傷害の抑制効果 (2016)
  • Author(s): 河島早紀、永田喜三郎、吉田雅幸、斉藤紀克、大澤肇、栗田克己、石神昭人
  • Organizer: 日本ビタミン学会第68回大会
  • Place of Presentation: 富山国際会議場, 富山市, 富山県
  • Year and Date: 2016-06-17
• [Presentation] ダブルノックアウトマウスは酸化ストレスが増加して脂肪肝を呈する (2016)
  • Author(s): 近藤嘉高、増冨裕文、野田義博、小澤裕介、高橋経太、半田節子、丸山直記、清水孝彦、石神昭人
  • Organizer: 日本基礎老化学会第39回大会
  • Place of Presentation: 神奈川県伊勢原市民文化会館（小ホール）, 伊勢原市, 神奈川県
  • Year and Date: 2016-05-27
• [Presentation] Senescence marker protein-30/Superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis. (2015)
  • Author(s): Ishigami, A., Kondo, Y., Masutomi, H., Noda, Y., Ozawa, Y., Takahashi, K., Maruyama, N., Shimizu, T.
  • Organizer: The 10th IAGG Asia/Oceania Regional Congress (IAGG 2015)
  • Place of Presentation: The International Convention and Exhibition Centre, Chiang Mai, Thailand
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] マウスの様々な臓器、血漿中のα-トコフェロール量及び肝臓でのα-トコフェロール輸送タンパク質（α-TTP）の加齢変化. (2015)
  • Author(s): 石神昭人、高橋経太、河野望、新井洋由
  • Organizer: 第18回Vitamin E Update Forum
  • Place of Presentation: 如水会館、千代田区、東京
  • Year and Date: 2015-08-28
  • Invited
• [Presentation] 胎児の発生や小児の成長におけるビタミンCの必要性. (2015)
  • Author(s): 石神昭人
  • Organizer: 第39回日本産科婦人科栄養・代謝研究会
  • Place of Presentation: 東京医科歯科大学、文京区、東京
  • Year and Date: 2015-08-22
  • Invited
• [Presentation] マウス臓器、血漿中のα-トコフェロール量及び肝臓α-トコフェロール輸送タンパク質の加齢変化. (2015)
  • Author(s): 高橋経太、下門顕太郎、河野 望、新井 洋由、石神昭人
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良春日野国際フォーラム甍、奈良市、奈良
  • Year and Date: 2015-06-05
• [Presentation] Vitamin C study using SMP30/GNL knockout mice. (2015)
  • Author(s): Ishigami, A.
  • Organizer: ACN2015
  • Place of Presentation: PACIFICO Yokohama, Yokohama, Japan
  • Year and Date: 2015-05-14
  • Int'l Joint Research / Invited
• [Remarks] ビタミンCの真実
  • URL: http://www.vit-c.jp/index.php