Cold-resistant and anti-arrhythmic adaptation of the heart in mice under energy restriction, and prolongation of their life span

• Project/Area Number: 15590526
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Hyogo College of Medicine
• Principal Investigator: WADA Yasuhiko Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10261653)
• Co-Investigator(Kenkyū-buntansha): IGUCHI Hiroshi Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (90025643) ; NISHIIKE Tamako Otemae College, Assistant professor, 講師 (40309448) ; NISHIMURA Yasumitsu Kawasaki Medical School, Faculty of Medicine, Assistant professor, 医学部, 講師 (90360271)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: Energy restriction / Hibernation / Electrocardiogram / Heart rate / Hypothermia / Circadian rhythm / Gene expression / Autonomic nerve / 老化制御 / イオンチャンネル / イオンポンプ / 心筋 / 筋原繊維

Research Abstract

Energy restriction (ER) without malnutrition has been known to retard aging processes and extend the life span in various species of mammals. We investigated the effects of ER on gene expression and physiological properties of the heart of C57Bl/6 male mice using AKITA diet. We analyzed the expression of heart mRNA from ER (200 kJ/week) or control (Ct) (400 kJ/week) B6 7-month-old male mice using cDNA microarray covering 6400 genes. mRNAs of 67 genes were increased and those of 153 genes were decreased by ER. It is suggested that the micro-structure and electro-physiological properties of the ER heart may change to adapt low energy and low temperature.
Ambulatory long-term recording of body temperature and electrocardiogram of aged mice revealed that the heart rate of ER mice changed up and down before body temperature did (i.e. hysteresis was observed). It means that the ER heart has an important role in changing body temperature. When body temperature decreased, the heart rate was dramatically decreased to one fifth and supra-ventricular arrhythmia was observed in ER mice, as in hibernators. ER did not change shapes of ECG waves. Analysis of heart rate variability revealed that parasympathetic activity was higher in ER than Ct mice. As aged, circadian rhythm of ER mice became obscure as Ct mice.
In conclusion, ER may alter structure and functional properties of the heart and make it adaptable to wide range of body temperature and energy availability. This also suggests that anti-arhythmic adaptation may occur in the heart of ER mice, which may contribute to the prolongation of their life span.

Research Products

• [Journal Article] Production of Nitric Oxide Elevates Nitrosothiol Formation Resulting in Decreased Glutathione in Macrophages Exposed to Asbestos or Asbestos Substitutes. (2005)
  • Author(s): Nishiike.T et al.
  • Journal Title: Arch. Toxicol. 79・2 Pages: 83-89
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Smoking cessation and mortality from cardiovascular disease among Japanese men and women : the JACC study. (2005)
  • Author(s): Iso H et al.
  • Journal Title: Am J Epidemiol. 161・2 Pages: 170-179
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Assessment of human exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in Japan using archived samples from the early 1980s and mid-1990s. (2005)
  • Author(s): Koizumi A et al.
  • Journal Title: Environ Res 99・1 Pages: 31-9
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Secular trends and geographical variations in the dietary intake of polybrominated diphenyl ethers (PBDEs) using archived samples from the early 1980s and mid 1990s in Japan. (2005)
  • Author(s): Wada Y et al.
  • Journal Title: J Occup Health 47・3 Pages: 236-41
  • NAID: 110003723270
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Body mass index and mortality from cardiovascular disease among Japanese men and women : the JACC study. (2005)
  • Author(s): Cui R et al.
  • Journal Title: Stroke 36・7 Pages: 1377-82
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Walking and sports participation and mortality from coronary heart disease and stroke. (2005)
  • Author(s): Noda H et al.
  • Journal Title: J Am Coll Cardiol 46・9 Pages: 1761-7
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Production of Nitric Oxide Elevates Nitrosothiol Formation Resulting in Decreased Glutathione in Macrophages Exposed to Asbestos or Asbestos Substitutes. (2005)
  • Author(s): Nishiike, T., Nishimura, Y., Wada, Y., Iguchi, H.
  • Journal Title: Arch Toxicol 79 Pages: 83-89
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] JACC Study Group. Smoking cessation and mortality from cardiovascular disease among Japanese men and women : the JACC Study. (2005)
  • Author(s): Iso H, Date C, Yamamoto A, Toyoshima H, Watanabe Y, Kikuchi S, Koizumi A, Wada Y, Kondo T, Inaba Y, Tamakoshi A
  • Journal Title: Am J Epidemiol 161 Pages: 170-179
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Assessment of human exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in Japan using archived samples from the early 1980s and mid-1990s. (2005)
  • Author(s): A Koizumi, T Yoshinaga, K Harada, K Inoue, A Morikawa, J Muroi, S Inoue, B Eslami, S Fujii, Y Fujimine, N Hachiya, S Koda, Y Kusaka, K Murata, H Nakatsuka, K Omae, N Saito, S Shimbo, K Takenaka, T Takeshita, H Todoriki, Y Wada, T Watanabe, M Ikeda
  • Journal Title: Environ Res 99 Pages: 31-39
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Secular trends and geographical variations in the dietary intake of polybrominated diphenyl ethers (PBDEs) using archived samples from the early 1980s and mid 1990s in Japan. (2005)
  • Author(s): Yasuhiko Wada, Akio Koizumi, Takeo Yoshinaga, Kouji Harada, Kayoko Inoue, Akiko Morikawa, Junko Muroi, Sumiko Inoue, Bita Eslami, Iwao Hirosawa, Akitsu Hirosawa, Shigeo Fujii, Yoshinori Fujimine, Noriyuki Hachiya, Shigeki Koda, Yukinori Kusaka, Katsuyuki Murata, Haruo Nakatsuka, Kazuyuki Omae, Norimitsu Saito, Shinichiro Shimbo, Katsunobu Takenaka, Tatsuya Takeshita, Hidemi Todoriki, Takao Watanabe, Masayuki Ikeda
  • Journal Title: J Occup Health 47 Pages: 236-241
  • NAID: 110003723270
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] JACC Study Group. Body mass index and mortality from cardiovascular disease among Japanese men and women : the JACC study. (2005)
  • Author(s): Cui R, Iso H, Toyoshima H, Date C, Yamamoto A, Kikuchi S, Kondo T, Watanabe Y, Koizumi A, Wada Y, Inaba Y, Tamakoshi A
  • Journal Title: Stroke 36 Pages: 1377-1378
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] JACC Study Group. Walking and sports participation and mortality from coronary heart disease and stroke. (2005)
  • Author(s): Noda H, Iso H, Toyoshima H, Date C, Yamamoto A, Kikuchi S, Koizumi A, Kondo T, Watanabe Y, Wada Y, Inaba Y, Tamakoshi A
  • Journal Title: J Am Coll Cardiol 46 Pages: 1761-1767
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] History of blood transfusion before 1990 is a risk factor for stroke and cardiovascular diseases : the Japan collaborative cohort study (JACC study). (2005)
  • Author(s): Yamada S et al.
  • Journal Title: Cerebrovasc Dis 20・3 Pages: 164-171
• [Journal Article] Large-scale evaluation of the current level of polybrominated diphenyl ethers (PBDEs) in breast milk from 13 regions of Japan. (2005)
  • Author(s): Eslami B et al.
  • Journal Title: Chemosphere (Epub)
• [Journal Article] Production of Nitric Oxide Elevates Nitrosothiol Formation Resulting in Decreased Glutathione in Macrophages Exposed to Asbestos or Asbestos Substitutes. (2005)
  • Author(s): Nishiike, T et al.
  • Journal Title: Arch.Toxicol. 79 Pages: 83-89
• [Journal Article] Smoking cessation and mortality from cardiovascular disease among Japanese men and women : the JACC Study. (2005)
  • Author(s): Iso H et al.
  • Journal Title: Am J Epidemiol. 161 Pages: 170-179
• [Journal Article] Assessment of human exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in Japan using archived samples from the early 1980s and mid-1990s. (2005)
  • Author(s): Koizumi A et al.
  • Journal Title: Environ Res (印刷中)
• [Journal Article] Secular trends and geographical variations in the dietary intake of polybrominated diphenyl ethers (PBDEs) using archived samples from the early 1980s and mid 1990s in Japan. (2005)
  • Author(s): Wada Y et al.
  • Journal Title: J Occup Health (印刷中)
  • NAID: 110003723270
• [Journal Article] Risk factors for fatal subarachnoid hemorrhage : The Japan Collaborative Cohort study. (2003)
  • Author(s): Yamada, S., et al.
  • Journal Title: Stroke 34・12 Pages: 2781-2787
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Risk factors for fatal subarachnoid hemorrhage : The Japan Collaborative Cohort study. (2003)
  • Author(s): Yamada S, Koizumi A, Iso H, Wada Y, Watanabe Y, Date C, Yamamoto A, Kikuchi S, Inaba Y, Toyoshima H, Kondo T, Tamakoshi A.
  • Journal Title: Stroke 34 Pages: 2781-2787
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 分子予防環境医学(分子予防環境医学研究会編)(老化) (2003)
  • Author(s): 和田安彦
  • Total Pages: 776
  • Publisher: 本の泉社
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamada, S., et al.: "Risk factors for fatal subarachnoid hemorrhage : The Japan Collaborative Cohort Study."Stroke. 34. 2781-2787 (2003)
• [Publications] 和田安彦: "分子予防環境医学(分子予防環境医学研究会編)(老化)"本の泉社. 776 (2003)