| Project/Area Number |
22510211
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical genome science
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| Research Institution | Osaka University |
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Principal Investigator |
KAMIDE Kei 大阪大学, 医学系研究科, 講師 (80393239)
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| Co-Investigator(Kenkyū-buntansha) |
樂木 宏実 (楽木 宏実 / 楽木 宏美) 大阪大学, 大学院・医学系研究科老年・腎臓内科学, 教授 (20252679)
勝谷 友宏 大阪大学, 大学院・医学系研究科寄附講座臨床遺伝子治療学, 特任准教授 (30311757)
大石 充 大阪大学, 大学院・医学系研究科老年・腎臓内科学, 講師 (50335345)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 遺伝素因 / 老化 / 健康長寿 / 生活習慣病 / ゲノム疫学研究 / 老化関連疾患 / 長寿関連遺伝子 / 一塩基多型 / 心血管疾患 |
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| Research Abstract |
We investigated the genetic influences of genes related to aging on successful aging. Recent findings from the genome-wide association studies have been pointing to novel disease-associated DNA regions, opening doors for new and more accurate targets of research and future therapies for several diseases.One of these new loci is the chromosome 9p21, which in first place was highlighted as the strongest genetic susceptibility locus for cardiovascular disease. Afterwards, this locus has been linked to other apparently unrelated conditions like cancer, type 2 diabetes, Alzheimer disease, frailty in the elderly, glaucoma, among others. Interestingly, this locus was considered gene deserted and only harbored a long non-coding RNA (called ANRIL) which function was unknown. Throughout our research in Osaka University, we were able to make significant progress in the understanding of the mechanism behind the 9p21 association. We studied the effects of ANRIL in vascular smooth muscle cells (which are directly involved in the pathogenesis of cardiovascular disease). After artificially reducing the expression of ANRIL (by siRNA) we proved a regulatory effect of the non coding RNA upon its neighbor genes CDKN2A/B, two important tumor suppressors, which main functions are to control cell growth and senescence. We also found a differential expression of ANRIL in senescent cells, which may imply a role of ANRIL in cell senescence and aging. We also clarified gene polymorphisms in ANRIL could be associated with Japanaese coronary diseases and reduced expression of ANRIL genes in peripheral blood might progress the atherosclerosis in human using human sample from our longevity study of an elderly cohort. Those important processes are certainly linked to atherosclerosis progression in human, but also are crucial in many other pathological conditions and might be the connection between the locus and several age-related human diseases.
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