Graduate School of Medicine „ Human Science
„ Aging Biology

@ : keiichih@shinshu-u.ac.jp

Professor: Keiichi HIGUCHI
Associate Professor: Masayuki MORI
Assistant Professor: Jinko SAWASHITA

Summary of Activity
  The long-term goal of research in our laboratory is to understand senescence of organism, and age-associated diseases.  Above all, we are interested in amyloidosis.  The amyloidoses constitute a large group of diseases including Alzheimer disease and prion diseases.  All forms of amyloidosis are caused by an alteration in the conformation and metabolism of several physiological@proteins into pathological insoluble fibrils (amyloid fibrils) which, under particular conditions, deposit extracellularly in various tissues.  The key in finding a cure and preventive measures for amyloidosis is, therefore, to clarify the mechanisms of amyloid fibril formation, and of deposition to specific organs and tissues.  To achieve this goal, we employ molecular genetic and biochemical techniques as well as various spontaneous, transgenic, and knockout mouse models.
  We are engaged in the studies for other age-associated diseases and common diseases as well.  We utilize senescence-accelerated mouse (SAM) strains, which are the models for accelerated senescence and various age-associated diseases.  We also specialize in molecular cloning of the causative genes in animal models for hereditary diseases.  In addition, we study the effects of exercise on common diseases in humans, such as obesity, hypertension, and dislipidemia.  Specific research interests include:


Research Projects
*Molecular biology of amyloidosis with special interest in the mechanisms for transmission of amyloidosis
*Molecular genetic mechanisms of senescence and lifespan by using senescence-accelerated mouse (SAM) strains
*Molecular cloning of the causative genes in mouse and rat models for hereditary diseases
*Molecular genetic basis of the therapeutic and preventive effects of exercise regimens on age-associated diseases in elderly people in conjunction with hMatsumoto city Jukunen Taiiku Daigakuh health promotion program
*Anti-aging effects of chemicals, antioxidants, and supplements
References
  1. Schmelzer C, Kubo H, Mori M, Sawashita J, Kitano M, Hosoe K, Boomgaaden I, Doring, F, Higuchi K. Supplementation with the reduced form of Coenzyme Q10 decelerates phenotypic characteristics of senescence and induces a PPAR-ƒΏ gene expression signature in SAMP1 mice. Mol Nutr Food Res 54(6): 805-815 (2010)

  2. Qian J, Yan J, Ge F, Zhang B, Fu X, Tomozawa H, Sawashita J, Mori M, Higuchi K. Mouse senile amyloid fibrils deposited in skeletal muscle exhibit amyloidosis-enhancing activity. PLoS Pathogens 6(5): e1000914 (2010)

  3. Zhang P, Fu X, Sawashita J, Yao J, Zhang B, Qian J, Tomozawa H, Mori M, Ando Y, Naiki H, Higuchi K. Mouse model to study human Aƒΐ2M amyloidosis: Generation of a transgenic mouse with excessive expression of human ƒΐ2-microglobulin. Amyloid 17(2): 50-62 (2010)

  4. Tomozawa H, Nishio A, Okuhara U, Higuchi K, Matsumoto K, Mori M. BN.MES-Cybames congenic rats manifest focal necrosis with eosinophilic infiltration in the liver without blood eosinophilia. Exp Animal 59(4): 469-478 (2010)

  5. Mori M, Higuchi K, Sakurai A, Tabara Y, Miki T, Nose H. Genetic basis of inter-individual variability in the effects of exercise on the alleviation of lifestyle-related diseases. J Physiol 587(Pt 23): 5577-8554 Review (2009)

  6. Sawashita J, Onitsuka S, Gen-no H, Ishikawa S, Iino F, Tateishi N, Murakami T, Seki Y, Nagaiwa T, Hanaoka M, Hama S, Nose H, Higuchi K. Effects of mild calorie restriction and high-intensity interval walking in middle-aged and older overweight Japanese. Exp Gerontol 44(10): 666-675 (2009)

  7. Sawashita J, Kametani F, Hasegawa K, Tsutsumi-Yasuhara S, Zhang B, Yan J, Mori M, Naiki H, Higuchi K. Amyloid fibrils formed by selective N-, C-terminal sequences of mouse apolipoprotein A-II. Biochim Biophys Acta-Proteins and Proteomics 1794(10): 1517-1529 (2009)

  8. Mori M, Li G, Hashimoto M, Nishio A, Tomozawa H, Suzuki N, Usami S, Higuchi K, Matsumoto K. Pivotal Advance: Eosinophilia in the MES rat strain is caused by a loss-of-function mutation in the gene for cytochrome b(-245), alpha polypeptide (Cyba). J Leukoc Biol 86(3): 473-478 (2009)

  9. Mori M, Fu X, Chen L, Zhang G, Higuchi K. Hereditary pancreatitis model WBN/Kob rat strain has a unique haplotype in the Pdwk1 region on chromosome 7. Exp Anim 58(4): 409-413 (2009)

  10. Zhang B, Une Y, Fu X, Yan J, Ge F, Yao J, Sawashita J, Tomozawa H, Kametani F, Higuchi K. Fecal translation of AA amyloidosis in the cheetah contributions to high incidence of disease. Proc Nat Acad Sci USA 105(20): 7263-7268 (2008)