| Project/Area Number |
15590328
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Human pathology
|
|---|
| Research Institution | Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare |
|---|
Principal Investigator |
TAKUBO Kaiyo Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Leader, 福祉振興財団・東京都老人総合研究所(高齢者の臓器と組織の研究グループ), 参事研究員 (00154956)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIMOMURA Naotaka Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Research associate, 福祉振興財団・東京都老人総合研究所(高齢者の臓器と組織の研究グループ), 助手 (10158751)
NAKAMURA Ken-ichi Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Tokyo Metropolitan Institute of Gerontology, Research associate, 福祉振興財団・東京都老人総合研究所(高齢者の臓器と組織の研究グループ), 助手 (60159069)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | telomere / talomerase / Werner's syndrome / テロメレース / 早期老化症候群 / 老化 / hTERT / 表皮 / 真皮 |
|---|
| Research Abstract |
We collected tissue samples from 7 different patients with Werner syndrome, two of whom provided samples on two different dates, giving a total of 9 samples. In these and control tissues, telomere length was measured by Southern blot analysis after digestion by Hinf I and Rsa I. Telomerase activity was examined by the TRAP assay and ISH. Telomere lengths measured using Hinf I and Rsa I were well correlated. Mean telomere length in the epidermis of 8 normal neonates was 13.3 kbp and the rate of reduction of telomere length for the epidermis was 36 bp/y. In the patients with Werner syndrome, the yearly rate of reduction of telomere length was 161 bp, which was estimated to be about 5 times the reduction rate for normal epidermis. In the 2 Werner patients who provided tissue samples on different dates, the yearly rates of reduction of telomere length in the tissues obtained were also higher than those for corresponding samples from controls. Telomere lengths were 7.0-12.8 kbp (39-61 y) for striated muscle fibers, 8.5 kbp (61 y) for bone marrow, 10.8 kbp (61 y) for cartilage, 5.6 kbp (61 y) for marginal epidermis surrounding a skin ulcer, and 11.5 kbp (41 y) for fibroblasts. Telomerase activity was present in 8% of epidermal samples from normal controls and in one sample of epidermis from Werner syndrome. hTERT mRNA expression was observed in epidermal basal cells, endothelial cells, and lymphocytes. We have been able to maintain 2 strains of epidermis and fibroblasts in culture. Based on our results, we have demonstrated for the first time that telomere shortening is more rapid in patients with Werner syndrome than in normal individuals. We have also successfully devised an original method for measuring telomere length in routinely prepared tissue sections by FISH.
|
