Life Science and Biotechnology (Age Dimension Research Center)

The primary mission of the Age Dimension Research Center (ADRC) is to pioneer an original field of research related to the molecular mechanisms of age-related homeostatis of physiological systems. The knowledge obtained through these research activities will be used for developing a new field, Age Dimension Technology (ADT), which facilitates generation of useful industrial technologies. With these research activities, ADRC contribute to strengthen the scientific and technological bases of the industrial Japanese society, which faces a rapid trend toward low birthrate/greater longevity.

Toward establishing the molecular mechanisms of age-related homeostatis, ADRC conducts detailed studies on the recently discovered ASE/AIE mediated age-axis regulatory mechanism of gene expression, the first age-related homeostasis mechanism. Liver nuclear proteins, which bind to key genetic elements, ASE and AIE, have been identified, and the first human disease in which the ASE/AIE mediated mechanism plays a critical role has also been identified. These achievements further strengthen the foundation of ADT.

Global analysis of age-related changes in protein expression provides an invaluable platform information for comprehensive understanding of age dimension homeostasis. As the first important step toward achieving this goal, a global analysis of age-related changes in expression of mouse liver nuclear proteins has been completed. Analyses of cytosolic protein expression changes as well as gender-related differences are also under way. These achievements will make an invaluable contribution to elucidation of the control mechanism of the life-span, age-related homeostasis.

ADRC is constructing a comprehensive database (DB) for age-related changes in the expression of liver nuclear proteins, the first of its kind in the world. Its prototype will become public in the very near future. This resource will serve as a valuable platform information for many areas of research and applications including basic studies on the molecular mechanisms underlying physiological homeostasis, epigenetic effects and drug evaluation.

Our past discovery of hepsin, a type II membrane protease, and subsequent demonstration of its high expression in the prostate cancer facilitated today's active hepsin research world-wide. In continuing this line of original efforts, DRDC recently,discovered that hepsin has a critical role in the network involved in generation of PSA, a common early diagnostic marker for prostate cancer.

ADRC also discovered an important correlation, in which plasmacytoid dendritic cells in Peyer's patches of the small intestine decrease with increasing age and induction of oral Immunological tolerance becomes less effective.
A Nod family genetic alteration, which correlates with a high frequency of sarcoidosis, was identified, and reduction of immunological response of the Nod family to the causative P.acnes bacteria was clarified.
DRDC also found that the complex route selection for affinity maturation of antibodies can be judged from the structural features of the antibodies in the initial repertory stage.
ADRC discovered that EAAC1, which has an important function on glutamic acid incorporation by nerve cells, is controlled by the interaction of addicsin and its binding protein, Arl6ip-l.
Finally, the DNA-binding domain structure and binding modality of SATB1, which is a factor controlling differentiation of immune T cells, were elucidated.