Evaluation of senescence markers for lifestyle-related disease

• Project/Area Number: 25670382
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Niigata University
• Principal Investigator: MINAMINO Tohru 新潟大学, 医歯学系, 教授 (90328063)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 老化 / p53 / テロメア / p21 / 早老症

Outline of Final Research Achievements

We could obtain the valid data of SNP genotyping and T/S ratio as mean LTL in 363 patients. Mean LTL was significantly longer in women than in men and inversely associated with age. Adjusted with age and sex, mean LTL had proportionately associations with total cholesterol and LDL-cholesterol levels, whereas serum creatinine level was negatively correlated with mean LTL. We identified minor alleles of FOXO1 encoding forkhead box O1 protein (rs2755213) was associated with shorter mean LTL. Analyses of patients who admitted to Niigata University Hospital showed that p53 expression was related to age and that p21 expression was significantly increased in patients with atherosclerosis. These results suggest that these molecular markers are useful for treatment of patients with lifestyle-related disease.

Research Products

• [Journal Article] Pathological Role of Adipose Tissue Dysfunction in Cardio-Metabolic Disorders. (2015)
  • Author(s): Shimizu I, Yoshida Y, Minamino T.
  • Journal Title: Int Heart J Volume: 印刷中
  • NAID: 130005070025
  • Peer Reviewed / Open Access
• [Journal Article] Electrocardiographic abnormalities and risk of developing cardiac events in extracardiac sarcoidosis. (2015)
  • Author(s): Nagao S, Watanabe H, Sobue Y, Kodama M, Tanaka J, Tanabe N, Suzuki E, Narita I, Watanabe E, Aizawa Y, Minamino T.
  • Journal Title: Int J Cardiol Volume: 189 Pages: 1-5
  • DOI: 10.1016/j.ijcard.2015.03.175
  • Peer Reviewed / Open Access
• [Journal Article] Liver Congestion in Heart Failure Contributes to Inappropriately Increased Serum Hepcidin despite Anemia (2015)
  • Author(s): Ohno Y, Hanawa H, Jiao S, Hayashi Y, Yoshida K, Suzuki T, Kashimura T, Obata H, Tanaka K, Watanabe T, Minamino T.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 235 Issue: 1 Pages: 69-79
  • DOI: 10.1620/tjem.235.69
  • NAID: 130004822430
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling. (2015)
  • Author(s): Sumida T, Naito AT, Nomura S, Nakagawa A, Higo T, Hashimoto A, Okada K, Sakai T, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Minamino T, Offermanns S, Noda T, Botto M, Kobayashi Y, Morita H, Manabe I, Nagai T, Shiojima I, Komuro I.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 6241-6241
  • DOI: 10.1038/ncomms7241
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of neoplastic cardiac tamponade and prognosis after pericardiocentesis: a single-center study of 113 consecutive cancer patients. (2015)
  • Author(s): Takayama T, Okura Y, Okada Y, Honma K, Nashimoto A, Sato N, Yokoyama A, Minamino T.
  • Journal Title: Int J Clin Oncol Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] DNA damage response and metabolic disease. (2014)
  • Author(s): Shimizu I, Yoshida Y, Suda M, Minamino T.
  • Journal Title: Cell Metab Volume: 20 Issue: 6 Pages: 967-977
  • DOI: 10.1016/j.cmet.2014.10.008
  • Peer Reviewed / Open Access
• [Journal Article] A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis. (2014)
  • Author(s): Ito TK, Yokoyama M, Yoshida Y, Nojima A, Kassai H, Oishi K, Okada S, Kinoshita D, Kobayashi Y, Fruttiger M, Aiba A, Minamino T.
  • Journal Title: PLoS One Volume: 9 Issue: 7 Pages: e102186-e102186
  • DOI: 10.1371/journal.pone.0102186
  • Peer Reviewed / Open Access
• [Journal Article] Relative refractoriness of left ventricular contraction underlies human tachycardia-induced mechanical and electrical alternans. (2014)
  • Author(s): Kashimura T, Kodama M, Watanabe T, Tanaka K, Hayashi Y, Ohno Y, Obata H, Ito M, Hirono S, Hanawa H, Minamino T.
  • Journal Title: Pacing Clin Electrophysiol Volume: 37 Issue: 2 Pages: 197-206
  • DOI: 10.1111/pace.12230
  • Peer Reviewed / Open Access
• [Journal Article] Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. (2014)
  • Author(s): Kitada K, Nakano D, Ohsaki H, Hitomi H, Minamino T, Yatabe J, Felder RA, Mori H, Masaki T, Kobori H, Nishiyama A.
  • Journal Title: J Diabetes Complications Volume: 28 Issue: 5 Pages: 604-611
  • DOI: 10.1016/j.jdiacomp.2014.05.010
  • Peer Reviewed / Open Access
• [Journal Article] Emerging issues in radiogenic cataracts and cardiovascular disease. (2014)
  • Author(s): Hamada N, Fujimichi Y, Iwasaki T, Fujii N, Furuhashi M, Kubo E, Minamino T, Nomura T, Sato H.
  • Journal Title: J Radiat Res Volume: 55 Issue: 5 Pages: 831-846
  • DOI: 10.1093/jrr/rru036
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of endothelial p53 improves metabolic abnormalities related to dietary obesity. (2014)
  • Author(s): Yokoyama M, Okada S, Nakagomi A, Moriya J, Shimizu I, Nojima A, Yoshida Y, Ichimiya H, Kamimura N, Kobayashi Y, Ohta S, Fruttiger M, Lozano G, Minamino T.
  • Journal Title: Cell Rep Volume: 7 Issue: 5 Pages: 1691-1703
  • DOI: 10.1016/j.celrep.2014.04.046
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of TERT in heterochromatin maintenance. (2014)
  • Author(s): Maida Y, Yasukawa M, Okamoto N, Ohka S, Kinoshita K, Totoki Y, Ito TK, Minamino T, Nakamura H, Yamaguchi S, Shibata T, Masutomi K.
  • Journal Title: Mol Cell Biol Volume: 印刷中 Issue: 9 Pages: 1576-1593
  • DOI: 10.1128/mcb.00093-14
  • Peer Reviewed / Open Access
• [Journal Article] Inappropriate expression of hepcidin by liver congestion contributes to anemia and relative iron deficiency. (2014)
  • Author(s): Suzuki T, Hanawa H, Jiao S, Ohno Y, Hayashi Y, Yoshida K, Kashimura T, Obata H, Minamino T.
  • Journal Title: J Card Fail Volume: 20 Issue: 4 Pages: 268-277
  • DOI: 10.1016/j.cardfail.2014.01.008
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of bepridil to prevent ventricular fibrillation in severe form of early repolarization syndrome (2014)
  • Author(s): Katsuumi G, Shimizu W, Watanabe H, Noda T, Nogami A, Ohkubo K, Makiyama T, Takehara N, Kawamura Y, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M, Aizawa Y, Makita N, Minamino T
  • Journal Title: Int J Cardiol Volume: 172 Issue: 2 Pages: 519-522
  • DOI: 10.1016/j.ijcard.2014.01.036
  • Peer Reviewed / Open Access
• [Journal Article] Augmentation of the J wave by rapid pacing in a patient with vasospastic angina. (2014)
  • Author(s): Sato A, Watanabe H, Sonoda K, Chinushi M, Tsuda T, Izumi D, Furushima H, Minamino T.
  • Journal Title: Int J Cardiol. Volume: 172 Issue: 1 Pages: e111-e113
  • DOI: 10.1016/j.ijcard.2013.12.121
  • Peer Reviewed / Open Access
• [Journal Article] Notch signaling regulates the lifespan of vascular endothelial cells via a p16-dependent pathway. (2014)
  • Author(s): Yoshida Y, Hayashi Y, Suda M, Tateno K, Okada S, Moriya J, Yokoyama M, Nojima A, Yamashita M, Kobayashi Y, Shimizu I, Minamino T.
  • Journal Title: PLoS One Volume: 20 Issue: 6 Pages: e100359-e100359
  • DOI: 10.1371/journal.pone.0100359
  • Peer Reviewed / Open Access
• [Journal Article] Arachidonate 12/15-lipoxygenase-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy. (2014)
  • Author(s): Suzuki H, Kayama Y, Sakamoto M, Iuchi H, Shimizu I, Yoshino T, Katoh D, Nagoshi T, Tojo K, Minamino T, Yoshimura M, Utsunomiya K.
  • Journal Title: Diabetes Volume: 64 Issue: 2 Pages: 618-630
  • DOI: 10.2337/db13-1896
  • Peer Reviewed / Open Access
• [Journal Article] Short QT syndrome in a boy diagnosed on screening for heart disease. (2014)
  • Author(s): Suzuki H, Hoshina S, Ozawa J, Sato A, Minamino T, Aizawa Y, Saitoh A.
  • Journal Title: Pediatr Int. Volume: 56 Issue: 5 Pages: 774-774
  • DOI: 10.1111/ped.12308
  • Peer Reviewed / Open Access
• [Journal Article] Inhibition of endothelial p53 improves metabolic abnormalities related to dietary abesity. (2014)
  • Author(s): Yokoyama M,Nakagomi A,Moriya J,Shimizu I,Nojima a,Yoshida Y,Ichimiya H,Kamimura N,Kobayashi Y,Ohta S,Fruttiger M,Lozano G,Minamino T.
  • Journal Title: Cell Reports Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia. (2013)
  • Author(s): Watanabe H, van der Werf C, Horie M. et al.
  • Journal Title: Heart Rhythm Volume: 10 Issue: 4 Pages: 542-547
  • DOI: 10.1016/j.hrthm.2012.12.035
  • Peer Reviewed
• [Journal Article] Tumor suppressor p53 inhibits systemic autoimmune diseases by inducing regulatory T cells. (2013)
  • Author(s): Kawashima H, Takatori H, Suzuki K, Iwata A, Yokota M, Suto A, Minamino T, Hirose K, Nakajima H
  • Journal Title: J Immunol. Volume: 19 Issue: 7 Pages: 3614-3623
  • DOI: 10.4049/jimmunol.1300509
  • Peer Reviewed
• [Journal Article] Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells (2013)
  • Author(s): Ozasa Y, Akazawa H, Qin Y, Tateno K, Ito K, Kudo-Sakamoto Y, Yano M, Yabumoto C, Naito AT, Oka T, Lee JK, Minamino T, Nagai T, Kobayashi Y, Komuro I
  • Journal Title: Hypertens Res Volume: 36(10) Issue: 10 Pages: 859-65
  • DOI: 10.1038/hr.2013.52
  • Peer Reviewed
• [Journal Article] Semaphorin-induced inflammation contributes to insulin resistance in dietary obesity. (2013)
  • Author(s): Shimizu I, Yoshida Y, Moriya J, Nojima A, Uemura A, Kobayashi Y, Minamino T.
  • Journal Title: Cell Metab Volume: 18 Issue: 4 Pages: 491-504
  • DOI: 10.1016/j.cmet.2013.09.001
  • Peer Reviewed
• [Journal Article] Malfunction of cardiac resynchronization therapy due to subsequent fracture of the ring and tip conductors of a co-radial left ventricular bipolar lead. (2013)
  • Author(s): Sato A, Chinushi M, Izumi D, Furushima H, Minamino T.
  • Journal Title: Intern Med Volume: 52 Pages: 1189-93
  • NAID: 130003365633
  • Peer Reviewed
• [Journal Article] SCN5A mutation associated with ventricular fibrillation, early repolarization, and concealed myocardial abnormalities (2013)
  • Author(s): Watanabe H, Ohkubo K, Watanabe I, Matsuyama TA, Ishibashi-Ueda H, Yagihara N, Shimizu W, Horie M, Minamino T, Makita N
  • Journal Title: Int J Cardiol. Volume: 165 Issue: 2 Pages: e21-e23
  • DOI: 10.1016/j.ijcard.2012.10.074
  • Peer Reviewed
• [Journal Article] A mutant mRNA expression in an endomyocardial biopsy sample obtained from a patient with a cardiac variant of Fabry disease caused by a novel acceptor splice site mutation in the invariant AG of intron 5 of the α-galactosidase A gene. (2013)
  • Author(s): Watanabe T, Hanawa H, Suzuki T, Jiao S, Yoshida K, Ogura M, Ohno Y, Hayashi Y, Ito M, Kashimura T, Obata H, Sato A, Ozawa T, Kodama M, Sakuraba H, Minamino T.
  • Journal Title: Intern Med. Volume: 52 Pages: 777-80
  • NAID: 130003365972
  • Peer Reviewed
• [Journal Article] Role of mutations in L-type calcium channel genes in Brugada syndrome, early repolarization syndrome, and idiopathic ventricular fibrillation associated with right bundle branch block. (2013)
  • Author(s): Watanabe H, Minamino T.
  • Journal Title: Circ J Volume: 77 Pages: 1689-90
  • NAID: 10031173746
  • Peer Reviewed
• [Journal Article] Haploinsufficiency of akt1 prolongs the lifespan of mice (2013)
  • Author(s): Nojima A, Yamashita M, Yoshida Y, Shimizu I, Ichimiya H, Kamimura N, Kobayashi Y, Ohta S, Ishii N, Minamino T
  • Journal Title: PLoS One Volume: 8(7) Issue: 7 Pages: e69178-e69178
  • DOI: 10.1371/journal.pone.0069178
  • Peer Reviewed
• [Journal Article] Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death. (2013)
  • Author(s): Bezzina CR, Makita N(63人中31番目)et al
  • Journal Title: Nat Genet. Volume: 45 Issue: 9 Pages: 1044-1049
  • DOI: 10.1038/ng.2712
  • Peer Reviewed / Open Access
• [Presentation] Role of senescence-associated inflammation in lifestyle-related disease. (2015)
  • Author(s): Minamino T.
  • Organizer: 2015 Seoul Symposium on Obesity & Diabetes
  • Place of Presentation: Seoul National University Hospital (韓国)
  • Year and Date: 2015-03-28
  • Invited
• [Presentation] Capillary rarefaction mediates whitening of brown fat and contributes to insulin resistance in obesity. (2014)
  • Author(s): Shimizu I, Walsh K, Minamino T.
  • Organizer: The 58th Annual Scientific Meeting of The Korean Society of Cardiology.
  • Place of Presentation: Korea（韓国）
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] 加齢疾患における脂肪不全の意義 (2014)
  • Author(s): 清水逸平，吉田陽子，Kenneth Walsh，南野 徹
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2014-11-25
  • Invited
• [Presentation] Molecular analysis of fat accumulation from the aspect of aging signals. (2014)
  • Author(s): Minamino T.
  • Organizer: International Symposium for the Study of Obesity.
  • Place of Presentation: シーガイアコンベンションセンター（Miyazaki）
  • Year and Date: 2014-10-26
  • Invited
• [Presentation] A critical role of senescence-induced inflammation in cardiovascular disease. (2014)
  • Author(s): Minamino T.
  • Organizer: 第18回日本心不全学会 日本&台湾セッション
  • Place of Presentation: 大阪国際会議場（大阪）
  • Year and Date: 2014-10-11
  • Invited
• [Presentation] 老化の観点から生活習慣病を考える (2014)
  • Author(s): Minamino T.
  • Organizer: 第135回日本内科学会信越地方会特別講演
  • Place of Presentation: キッセイ文化ホール（松本）
  • Year and Date: 2014-10-04
  • Invited
• [Presentation] 細胞老化シグナルによる炎症制御と疾患 (2014)
  • Author(s): Minamino T.
  • Organizer: 第35回日本炎症・再生医学会シンポジウム
  • Place of Presentation: 万国津梁館（沖縄）
  • Year and Date: 2014-07-01 – 2014-07-04
  • Invited
• [Presentation] 老化再生からみた循環器疾患治療 (2014)
  • Author(s): Minamino T.
  • Organizer: 第32回日本臨床化学会甲信越支部総会シンポジウム
  • Place of Presentation: 鵜の浜ニューホテル（上越）
  • Year and Date: 2014-06-29
  • Invited
• [Presentation] 細胞老化シグナルによる炎症制御と疾患 (2014)
  • Author(s): Minamino T.
  • Organizer: 第18回日本適応学会シンポジウム
  • Place of Presentation: 一橋大学一橋講堂（東京）
  • Year and Date: 2014-06-21 – 2014-06-22
  • Invited
• [Presentation] 健康寿命は延伸可能か？ (2014)
  • Author(s): Minamino T.
  • Organizer: 第14回日本抗加齢医学会シンポジウム
  • Place of Presentation: 大阪国際会議場（大阪）
  • Year and Date: 2014-06-06 – 2014-06-08
  • Invited
• [Presentation] The efficacy of combination therapy in patients with pulmonary hypertension. (2014)
  • Author(s): Minamino T.
  • Organizer: 3th International Pulmonary Hypertension Forum
  • Place of Presentation: リスボン（Portugal）
  • Year and Date: 2014-04-04 – 2014-04-06
  • Invited
• [Presentation] 臓器連関とインスリン感受性 (2013)
  • Author(s): Minamino T.
  • Organizer: 第86回日本内分泌学会総会シンポジウム
  • Place of Presentation: 仙台（仙台国際センター）
  • Invited
• [Presentation] Lifespan regulatory system as a potential therapeutic target for cardiovascular disease. (2013)
  • Author(s): Minamino T.
  • Organizer: International Association of Gerontology and Geriatrics
  • Place of Presentation: Seoul（韓国）
  • Invited
• [Presentation] 血管老化とNO (2013)
  • Author(s): Minamino T.
  • Organizer: 第13回日本抗加齢医学会ランチョンセミナー
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Invited
• [Presentation] Circadian clock and cardiovascular aging. (2013)
  • Author(s): Minamino T.
  • Organizer: IEEE EMBC
  • Place of Presentation: Osaka（大阪国際会議場）
  • Invited
• [Presentation] 心-脂肪連関による心不全発症のメカニズム (2013)
  • Author(s): Minamino T.
  • Organizer: 第17回日本心臓リハビリテーション学会シンポジウム
  • Place of Presentation: 仙台（仙台国際センター）
  • Invited
• [Presentation] Role of cellular aging signals in cardiovascular and metabolic disease. (2013)
  • Author(s): Minamino T.
  • Organizer: BCVS
  • Place of Presentation: Las Vegas（アメリカ）
  • Invited
• [Presentation] 老化シグナルネットワークによる循環代謝制御 (2013)
  • Author(s): Minamino T.
  • Organizer: 第86回日本生化学会大会シンポジウム
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Invited
• [Presentation] 血管老化シグナルネットワークによる循環代謝制御 (2013)
  • Author(s): Minamino T.
  • Organizer: 第21回日本血管生物医学会シンポジウム
  • Place of Presentation: 大阪（千里阪急ホテル）
  • Invited
• [Presentation] Role of senescence-associated inflammation in lifestyle-related disease.
  • Author(s): Minamino T.
  • Organizer: ISHR
  • Place of Presentation: San Diego（アメリカ）
  • Invited
• [Presentation] Role of cellular aging signals in lifestyle-related disease.
  • Author(s): Minamino T.
  • Organizer: Harbin Medical University
  • Place of Presentation: Harbin（中国）
  • Invited
• [Presentation] 次世代の血管新生治療の開発
  • Author(s): Minamino T.
  • Organizer: 第22回日本形成外科学会基礎学術集会
  • Place of Presentation: 新潟（朱鷺メッセ）
  • Invited
• [Presentation] 老化からみた心血管治療としてのスタチンの有用性
  • Author(s): Minamino T.
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 大宮（大宮ソニックシティー）
  • Invited
• [Presentation] 心血管系の老化のメカニズム
  • Author(s): Minamino T.
  • Organizer: 日本老年医学会 支部・地方会 第24回九州地方支部
  • Place of Presentation: 九州（産業医科大学）
  • Invited
• [Book] 抗凝固薬・高血小板薬 (2015)
  • Author(s): 和泉大輔、南野 徹
  • Publisher: 医薬ジャーナル社
• [Book] 虚血肢の再生治療 (2015)
  • Author(s): 南野 徹、須田将吉
  • Publisher: メディカルトリビューン社
• [Book] 重症心不全の患者さんが来ました (2015)
  • Author(s): 尾崎和幸、南野 徹
  • Publisher: 中外医学社
• [Book] 心不全 浮腫～塩・水過剰、新たな展開とは？ (2014)
  • Author(s): 小幡 裕明，南野 徹
  • Publisher: 医薬ジャーナル社
• [Book] 特集；遺伝性不整脈の診断とマネージメント -三大陸不整脈学会Expert Consensus Statementを踏まえて- (2014)
  • Author(s): 渡部 裕，南野 徹
  • Publisher: メディカルレビュー社
• [Book] インスリン抵抗性と心不全 (2013)
  • Author(s): 清水逸平，南野 徹
  • Publisher: 中外医学社
• [Book] 体内時計の分子機構と老化 時間薬理学による最新の治療戦略 (2013)
  • Author(s): 南野 徹
  • Publisher: 医薬ジャーナル社
• [Book] 慢性炎症と生活習慣病 (2013)
  • Author(s): 岡田将、南野 徹
  • Publisher: 南山堂
• [Book] 再生医療事業の課題解決のための手引書 (2013)
  • Author(s): 小澤拓也、南野 徹
  • Publisher: 株式会社技術情報協会
• [Book] 心不全や肥満における脂肪老化シグナルの意義 (2013)
  • Author(s): 清水逸平，南野 徹
  • Publisher: 診断と治療社
• [Remarks] 新潟大学大学院医歯学研究院循環器内科
  • URL: http://www.med.niigata-u.ac.jp/car/