Aging and Life Style-associated Diseases

Theme Leader :
Seijiro Mori, M.D., Ph.D.
Adjunct Researcher :
Heying Zhou, Ph.D.

Diabetes mellitus, genetic polymorphism, osteoporosis, sarcopenia, Werner syndrome

1. 1.Implementation of personalized medicine
2. 2.Discovery of susceptible genes for osteoporosis and sarcopenia
3. 3.Establishment of BioBank Japan
4. 4.Promotion of translational research

Life style-associated diseases such as metabolic syndrome, smoking-induced lung cancer, and so on, are considered to be caused mainly by environmental factors. Amelioration of the evil life style, i.e., to eat less, walk more, and cease smoking, for example, may be the best approach to prevent these diseases, however, under the identical circumstances, some people are suffering from them and others are not. Such kind of individual variation of susceptibility to the disease is generally attributed to genetic variations among the human being. Especially, a single nucleotide polymorphism seems to play an important role in determining a predisposition to the multi-factorial disease. As the research for exploring gene polymorphisms responsible for the onset of a disease is advanced, one would be able to easily pinpoint a high risk group for the disease just by using a drop of blood. And if so, it is expected to establish far more efficient and economically sound method, as compared with blindly comprehensive intervention to slash all of the possible risk factors, for the prevention of the disease.
Base on the above mentioned view, we are now promoting a couple of projects to seek for disease gene polymorphisms; genome-wide association study to identify genetic determinants for the onset of osteoporsosis, as well as a candidate gene approach to identify genetic determinants for skeletal muscle mass in senile sarcopenia.
Since our laboratory is founded on the hospital and consisted mainly of the hospital stuffs, we are also promoting a fundamental part of translational research activities in Tokyo Metropolitan Geriatric Hospital.

1. 1. Mori, S., Zhou, H., Yamaga, M., Takemoto, M., Yokote, K.: Femoral osteoporosis is more common than lumbar osteoporosis in patients with Werner syndrome. Geriatr. Gerontol. Int., in press.
2. 2. Honma, N., Saji, S., Mikami, T., Yoshimura, N., Mori, S., Saito, Y., Murayama, S., Harada, N.: Estrogen-related factors in the frontal lobe of Alzheimer's disease patients and importance of body mass index. Sci. Rep., 7(1): 726, 2017.
3. 3. Yamada, Y., Sakuma, J., Takeuchi, I., Yasukochi, Y., Kato, K., Oguri, M., Fujimaki, T., Horibe, H., Muramatsu, M., Sawabe, M., Fujiwara, Y., Taniguchi, Y., Obuchi, S., Kawai, H., Shinkai, S., Mori, S., Arai, T., Tanaka, M.: Identification of STXBP2 as a novel susceptibility locus for myocardial infarction in Japanese individuals by an exome-wide association study. Oncotarget, 8: 33527-33535, 2017.
4. 4. Tanisawa, K., Arai, Y., Hirose, N., Shimokata, H., Yamada, Y., Kawai, H., Kojima, M., Obuchi, S., Hirano, H., Yoshida, H., Suzuki, H., Fujiwara, Y., Ihara, K., Sugaya, M., Arai, T., Mori, S., Sawabe, M., Sato, N., Muramatsu, M., Higuchi, M., Liu, Y.W., Kong, Q.P., Tanaka, M.: Exome-wide association study identifies CLEC3B missense variant p.S106G as being associated with extreme longevity in east Asian populations. J. Gerontol. A. Biol. Sci. Med. Sci., 72: 309-318, 2017.
5. 5. Zaw, K.T.T., Sato, N., Ikeda, S., Thu, K.S., Mieno, M.N., Arai, T., Mori, S., Furukawa, T., Sasano, T., Sawabe, M., Tanaka, M., Muramatsu, M.: Association of ZFHX3 gene variation with atrial fibrillation, cerebral infarction, and lung thromboembolism: an autopsy study. J. Cardiol. 2016 Dec 19. pii: S0914-5087(16)30290-8. doi: 10.1016/j.jjcc.2016.11.005. [Epub ahead of print]
6. 6. Maeda, Y., Sato, N., Naka-Mieno, M., Mori, S., Arai, T., Tanaka, M., Muramatsu, M., Sawabe, M.: Association of non-synonymous variants in WIPF3 and LIPA genes with abdominal aortic aneurysm: an autopsy study. J. Geriatr. Cardiol., 13: 960-967, 2016.
7. 7. Thu, K.S., Sato, N., Ikeda, S., Naka-Mieno, M., Arai, T., Mori, S., Sawabe, M., Muramatsu, M., Tanaka, M.: Association of polymorphisms of the transporter associated with antigen processing (TAP2) gene with pulmonary tuberculosis in an elderly Japanese population. APMIS, 124: 675-680, 2016.
8. 8. Zhou, H., Mori, S., Ishizaki, T., Takahashi, A., Matsuda, K., Koretsune, Y., Minami,S., Higashiyama, M., Imai,S., Yoshimori, K., Doita, M., Yamada, A., Nagayama, S., Kaneko, K., Asai, S., Shiono, M., Kubo, M., Ito, H.: Genetic risk score based on the prevalence of vertebral fracture in Japanese women with osteoporosis. Bone Rep., 5: 168-172, 2016.
9. 9. Tamura, Y., Izumiyama-Shimomura, N., Kimbara, Y., Nakamura, K., Ishikawa, N., Aida, J., Chiba, Y., Matsuda, Y., Mori, S., Arai, T., Fujiwara, M., Poon, S.S., Ishizaki, T., Araki, A., Takubo, K., Ito, H.: Telomere attrition in beta and alpha cells with age. Age (Dordr), 38(3): 61, 2016.
10. 10. Zhou, H., Mori, S., Ishizaki, T., Tanaka, M., Tanisawa, K., Mieno, M.N., Sawabe, M., Arai, T., Muramatsu, M., Yamada, Y., Ito, H.: Genetic risk score based on the lifetime prevalence of femoral fracture in 924 consecutive autopsies of Japanese males. J. Bone Miner. Metab., 34: 685-691, 2016.
11. 11. Mori, S., Zhou, H.: Implementation of personalized medicine for fracture risk assessment in osteoporosis. Geriatr. Gerontol. Int., 16 (Suppl. 1): 57-65, 2016.
12. 12. Zhou, H., Mori, S., Tanaka, M., Sawabe, M., Arai, T., Muramatsu, M., Mieno, M.N., Shinkai, S., Yamada, Y., Miyachi, M., Murakami, H., Sanada, K., Ito, H.: A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese population. J. Bone Miner. Metab., 33: 694-700, 2015.
13. 13. Chiba, Y., Kimbara, Y., Kodera, R., Tsuboi, Y., Sato, K., Tamura, Y., Mori, S., Ito, H., Araki, A.: Risk factors associated with falls in elderly patients with type 2 diabetes. J. Diabetes Complications 29: 898-902, 2015.
14. 14. Nishizawa, D., Kasai, S., Hasegawa, J., Sato, N., Yamada, H., Tanioka, F., Nagashima, M., Katoh, R., Satoh, Y., Tagami, M., Ujike, H., Ozaki, N., Inada, T., Iwata, N., Sora, I., Iyo, M., Yamada, M., Kondo, N., Won, MJ., Naruse, N., Uehara-Aoyama, K., Itokawa, M., Ohi, K., Hashimoto, R., Tanisawa, K., Arai, T., Mori, S., Sawabe, M., Naka-Mieno, M., Yamada, Y., Yamada, M., Sato, N., Muramatsu, M., Tanaka, M., Irukayama-Tomobe, Y., Saito, Y., Sakurai, T., Hayashida, M., Sugimura, H., Ikeda, K. Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies. Mol. Brain 8: 50, 2015.
15. 15. Kim, M., Shinkai, S., Murayama, H., Mori, S.: Comparison of segmental multi-frequency bioelectrical impedance analysis with dual-energy X-ray absorptiometry for the assessment of body composition in community-dwelling older population. Geriatr. Gerontol. Int., 15: 1013-1022, 2015.
16. 16. Yamada, M., Sato, N., Ikeda, S., Arai, T., Sawabe, M., Mori, S., Yamada, Y., Muramatsu, M., Tanaka, M.: Association of the chromodomain helicase DNA-binding protein 4 (CHD4) missense variation p.D140E with cancer: potential interaction with smoking. Genes Chromosomes Cancer, 54: 122-128, 2015.