Molecular and Cellular Aging

Theme Leader :
Masataka Sugimoto, Ph.D.
Researcher :
Hiromichi Tsushima, Ph.D.

Cellular senescence, Senolysis, Pulmonary disease, COPD, Emphysema, Tumor suppressor

1. 1.Pathophysiological roles of cellular senescence in tissue aging and aging associated chronic diseases
2. 2.Establishment of a therapeutic model for age-related diseases targeting senescent cells

1. Pathophysiological roles of cellular senescence in tissue aging and aging associated chronic diseases
Cells undergo an irreversible cell cycle arrest called “cellular senescence” in response to various cellular insults. Senescent cells accumulate in tissues during aging and secrete a series of cytokines and tissue remodeling enzymes, namely “senescence-associated secretory phenotype (SASP)”, thereby affecting their surrounding environment. Aim of our study is to elucidate the mechanisms by which senescent cells are involved in the tissue aging and the pathogenesis of chronic diseases.
2. Establishment of a therapeutic model for chronic pulmonary diseases targeting senescent cells
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide, with an estimated prevalence of over 5 million people in Japan. Pulmonary emphysema is a main component of COPD, and there is currently no cure for this disease. Our studies have revealed that cellular senescence is involved in the exacerbation of the emphysema pathology. Therefore, we are aiming to establish an animal model for the treatment of emphysema that targets senescent cells.

1. 1.Kawaguchi K., Hashimoto M., Mikawa R., Asai A., Sato T., Sugimoto M. Protocol for assessing senescence-associated lung pathologies in mice. STAR Protocols 2. 100993. 2021.
2. 2.Suda M., Shimizu I., Katsuumi G., Yoshida Y., Hayashi Y., Ikegami R., Matsumoto N., Yoshida Y., Mikawa R., Katayama A., Wada J., Seki M., Suzuki Y., Iwama A., Nakagami H., Nagasawa A., Morishita R., Sugimoto M., Okuda S., Tsuchida M., Ozaki K., Nakanishi-Matsui M., Minamino T. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nature Aging 1. 1117-1126. 2021.
3. 3.Kawaguchi K., Komoda K., Mikawa R., Asai A., Sugimoto M. Cellular senescence promotes cancer metastasis by enhancing soluble E-cadherin production. iScience 24. 103022. 2021.
4. 4.Kawaguchi K., Hashimoto M., Sugimoto M. An antioxidant suppressed lung cellular senescence and enhanced pulmonary function in aged mice. Biochem. Biophys. Res. Commun. 541. 43-49. 2021.
5. 5.Johmura Y., Yamanaka T., Omori S., Wang T.W., Sugiura Y., Matsumoto M., Suzuki N., Kumamoto S., Yamaguchi K., Hatakeyama S., Takami T., Yamaguchi R., Shimizu E., Ikeda K., Okahashi N., Mikawa R., Suematsu M., Arita M., Sugimoto M., Nakayama K.I., Furukawa Y., Imoto S., Nakanishi M. Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science 371. 265-270. 2021.
6. 6.Mikawa R., Sato T., Suzuki Y., Baskoro H., Kawaguchi K., Sugimoto M. p19Arf exacerbates cigarette smoke-induced lung dysfunction. Biomolecules 10. E462. 2020.
7. 7.Mikawa R., Suzuki Y., Baskoro Y., Kanayama K., Sugimoto K., Sato T., Sugimoto M. Elimination of p19ARF-expressing cells protects against pulmonary emphysema in mice. Aging Cell 30. e12827. 2018.
8. 8.Suzuki Y., Sato T., Sugimoto M., Baskoro H., Karasutani K., Mitsui A., Nurwidya F., Arano N., Kodama Y., Hirano SI., Ishigami A., Seyama K. Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice. Biochem Biophys Res Commun. 492. 74-81. 2017.
9. 9.Hashimoto M., Asai A., Kawagishi H., Mikawa R., Iwashita Y., Kanayama K., Sugimoto K., Sato T., Maruyama M., and Sugimoto M. Elimination of p19ARF-expressing cells enhances pulmonary function in mice. JCI insight 1(12). e88057. 2016.