Interdisciplinary Advanced Research

Unraveling pathophysiology of progeroid syndrome and age related diseases
Professor Koutaro Yokote

Although it is well-known that the risk of lifestyle-related diseases and cancer increase with age, the underlying mechanisms remain unknown. In this study, we aim to elucidate the pathophysiology of progeroid syndrome, in which aging occurs more rapidly than expected and is frequently complicated by diabetes and cancer. We believe that our research will further lead us to understand human aging mechanisms.

Werner syndrome, the premature aging disease, causes gray hair, hair loss, and cataracts in both eyes beginning in the 20s. Patients with this disease suffer from thinness and hardness of the muscles and skin, coupled with the appearance of rapid aging. The disease is common among the Japanese population, and 60% of the world's reports of this condition are from Japan. However, the estimated number of patients with Werner syndrome in Japan is only 700?2,000, making it a rare condition. Therefore, many cases of Werner syndrome are not diagnosed or are inadequately treated. As a result, many patients face great difficulties in their daily lives.

Werner syndrome is known to be caused by a mutation in a RecQ type helicase Warner Syndrome Gene (WRN), an enzyme involved in DNA replication and repair. Typically, a mouse model, called a knockout mouse, in which the gene that causes the disease is destroyed, is used to elucidate the mechanism and develop treatment for a disease. Research, however, has not progressed as expected, since WRN gene knockout mice do not show a premature aging phenotype. Therefore, we are developing a primate model of Werner syndrome by targeting the WRN gene in small primates called marmosets. We hope to clarify the mechanism of aging and age-related diseases by using our new primate model as well as induced pluripotent stem cells, also known as iPS cells, derived from patients with Werner syndrome, which we have already established.