Elucidation of molecular pathology of aging and diseases based on multi-dimensional analysis of progeroid syndromes

• Project/Area Number: 17H01558
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Chiba University
• Principal Investigator: Yokote Koutaro 千葉大学, 大学院医学研究院, 教授 (20312944)
• Co-Investigator(Kenkyū-buntansha): 竹本 稔 千葉大学, 大学院医学研究院, 特任教授 (60447307) ; 前澤 善朗 千葉大学, 大学院医学研究院, 講師 (80436443) ; 清水 孝彦 千葉大学, 大学院医学研究院, 講師 (40301791)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥43,160,000 (Direct Cost: ¥33,200,000、Indirect Cost: ¥9,960,000); Fiscal Year 2019: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2018: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000); Fiscal Year 2017: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
• Keywords: 早老症 / ウェルナー症候群 / 動脈硬化 / マーモセット / 老年医学 / iPS細胞 / 間葉系幹細胞 / 分化 / 老化

Outline of Final Research Achievements

Werner syndrome is one of the progeroid syndromes that show gray hair, bilateral cataract, diabetes, arteriosclerosis and malignant tumors early after puberty. In this study, we tried to elucidate the pathological mechanism of Werner syndrome using various techniques.
Mesenchymal stem cells, adipocytes and blood vessel cells differentiated from Werner syndrome iPS cells show early aging symptoms. Wrn KO mice did not show any progeroid phenotype, but double knockout mice with another RecQ helicase of the same molecular family exhibit obesity and impaired glucose tolerance. These observation will shed new light on the molecular mechanism of Werner syndrome and general aging.

Academic Significance and Societal Importance of the Research Achievements

Werner症候群は遺伝子病であり現時点で根本的な治療法がない。このため、本疾患の患者は早発する動脈硬化や、悪性腫瘍、極めて強い痛みを伴う難治性皮膚潰瘍に苦しんでいる。本研究により早期老化の機序が解明されれば、新規治療法開発につながる可能性がある。また、Werner症候群の老化徴候は一般老化と共通点が多く、糖尿病や動脈硬化、癌など一般的な老化関連疾患のメカニズム解明にも資する知見が得られることが期待される。

Research Products

• [Int'l Joint Research] 米国国立老化研究所(米国)
• [Int'l Joint Research] University of Washington/国立老化研究所(米国)
• [Int'l Joint Research] University of Washington(米国)
• [Journal Article] Dose‐dependent reduction in body weight with LIK066 (licogliflozin) treatment in Japanese patients with obesity (2020)
  • Author(s): Yokote Koutaro、Sano Misako、Tsumiyama Isao、Keefe Deborah
  • Journal Title: Diabetes, Obesity and Metabolism Volume: - Issue: 7 Pages: 1102-1110
  • DOI: 10.1111/dom.14006
  • Peer Reviewed
• [Journal Article] A case of generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement with short and long-term monitoring of the metabolic and endocrine profiles (2020)
  • Author(s): Fukaishi Takahiro、Minami Isao、Masuda Seizaburo、Miyachi Yasutaka、Tsujimoto Kazutaka、Izumiyama Hajime、Hashimoto Koshi、Yoshida Masayuki、Takahashi Sayako、Kashimada Kenichi、Morio Tomohiro、Kosaki Kenjiro、Maezawa Yoshiro、Yokote Koutaro、Yoshimoto Takanobu、Yamada Tetsuya
  • Journal Title: Endocrine Journal Volume: 67 Issue: 2 Pages: 211-218
  • DOI: 10.1507/endocrj.EJ19-0226
  • NAID: 130007802875
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Novel mechanism of increasing cerebral vascular constriction in acute hyperglycemia and diabetes through adenylyl cyclase 5‐generated cyclic adenosine monophosphate (2019)
  • Author(s): Sakamoto Kenichi、Yokote Koutaro
  • Journal Title: Journal of Diabetes Investigation Volume: - Issue: 4 Pages: 783-785
  • DOI: 10.1111/jdi.13186
  • Peer Reviewed
• [Journal Article] Background characteristics and postoperative outcomes of insufficient weight loss after laparoscopic sleeve gastrectomy in Japanese patients. (2019)
  • Author(s): Saiki A, Yamaguchi T, Tanaka S, Sasaki A, Naitoh T, Seto Y, Matsubara H, Yokote K, Okazumi S, Ugi S, Yamamoto H, Ohta M, Ishigaki Y, et al
  • Journal Title: Ann Gastroenterol Surg. Volume: 3 Issue: 6 Pages: 638-647
  • DOI: 10.1002/ags3.12285
  • Peer Reviewed / Open Access
• [Journal Article] NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome (2019)
  • Author(s): Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Kato H, et al.
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 1-8
  • DOI: 10.1038/s41467-019-13172-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Investigator‐initiated clinical study of a functional peptide, SR‐0379, for limb ulcers of patients with Werner syndrome as a pilot study (2019)
  • Author(s): Nakagami Hironori、Sugimoto Ken、Ishikawa Takahiro、Koshizaka Masaya、Yokote Koutaro、Rakugi Hiromi
  • Journal Title: Geriatrics & Gerontology International Volume: 19 Issue: 11 Pages: 1118-1123
  • DOI: 10.1111/ggi.13782
• [Journal Article] Efficacy and Safety of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα): Pooled Analysis of Phase 2 and 3 Studies in Dyslipidemic Patients with or without Statin Combination (2019)
  • Author(s): Yamashita、Arai、Yokote、Araki、Matsushita、Nojima、Suganami、Ishibashi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 22 Pages: 5537-5537
  • DOI: 10.3390/ijms20225537
  • Peer Reviewed / Open Access
• [Journal Article] Aldosterone reduction rate after saline infusion test may be a novel prediction in patients with primary aldosteronism. (2019)
  • Author(s): 27.Nagano H, Kono T, Saiga A, Kubota Y, Fujimoto M, Felizola S, Ishiwata K, Tamura A, Higuchi S, Sakuma I, Hashimoto N, Suzuki S, Koide H, Takeshita N, Sakamoto S, Ban T, Yokote K, Nakamura Y, Ichikawa T, Uno T, Tanaka T.
  • Journal Title: J Clin Endocrinol Metab. Volume: 19 Issue: 3 Pages: 319-327
  • DOI: 10.1210/clinem/dgz092
  • Peer Reviewed / Open Access
• [Journal Article] A case of Hashimoto’s thyroiditis with multiple drug resistance and high expression of efflux transporters. (2019)
  • Author(s): Yoshida T, Nakayama A, Tamura A, Higuchi S, Sakuma I, Nagano H, Saulo J.A. Felizola, Takemoto M, Tatsuno I, Koide H, Yokote K, Tanaka T.
  • Journal Title: J Clin Endocrinol Metab. Volume: 105 Issue: 2 Pages: 399-406
  • DOI: 10.1210/clinem/dgz073
  • Peer Reviewed / Open Access
• [Journal Article] Pharmacokinetics and exploratory efficacy biomarkers of bococizumab, an anti-PCSK9 monoclonal antibody, in hypercholesterolemic Japanese subjects (2019)
  • Author(s): Yokote Koutaro、Suzuki Akiyuki、Li Yinhua、Matsuoka Nobushige、Teramoto Tamio
  • Journal Title: Int. Journal of Clinical Pharmacology and Therapeutics Volume: 57 Issue: 12 Pages: 575-589
  • DOI: 10.5414/cp203418
• [Journal Article] R3hdml regulates satellite cell proliferation and differentiation (2019)
  • Author(s): Sakamoto Kenichi、Furuichi Yasuro、Yamamoto Masashi、Takahashi Megumi、Akimoto Yoshihiro、Ishikawa Takahiro、Shimizu Takahiko、Fujimoto Masanori、Takada‐Watanabe Aki、Hayashi Aiko、Mita Yoshitaka、Manabe Yasuko、Fujii Nobuharu L、Ishibashi Ryoichi、Maezawa Yoshiro、Betsholtz Christer、Yokote Koutaro、Takemoto Minoru
  • Journal Title: EMBO reports Volume: 20 Issue: 11 Pages: 1-12
  • DOI: 10.15252/embr.201947957
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multidrug use positively correlates with high-risk prescriptions in the Japanese elderly: a longitudinal study (2019)
  • Author(s): Arai Sayaka、Ishikawa Takahiro、Kato Hisaya、Koshizaka Masaya、Maezawa Yoshio、Nakamura Takako、Suzuki Takaaki、Yokote Koutaro、Ishii Itsuko
  • Journal Title: Journal of Pharmaceutical Health Care and Sciences Volume: 5 Issue: 1
  • DOI: 10.1186/s40780-019-0150-6
• [Journal Article] KDM2B in polycomb repressive complex 1.1 functions as a tumor suppressor in the initiation of T-cell leukemogenesis. (2019)
  • Author(s): Isshiki Y, Nakajima-Takagi Y, Oshima M, Aoyama K, Rizk M, Kurosawa S, Saraya A, Kondo T, Sakaida E, Nakaseko C, Yokote K, Koseki H, Iwama A.
  • Journal Title: Blood Adv Volume: 3 Issue: 17 Pages: 2537-2549
  • DOI: 10.1182/bloodadvances.2018028522
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75) (2019)
  • Author(s): Ouchi Yasuyoshi、Sasaki Jun、Arai Hidenori、Yokote Koutaro et al.
  • Journal Title: Circulation Volume: 140 Issue: 12 Pages: 992-1003
  • DOI: 10.1161/circulationaha.118.039415
• [Journal Article] Residual vascular risk in diabetes ? Will the SPPARM alpha concept hold the key? (2019)
  • Author(s): Fruchart Jean-Charles、Santos Raul D.、Yamashita Shizuya、Libby Peter、Fruchart Jean-Charles、Santos Raul D.、Yamashita Shizuya、Aikawa Masanori、Libby Peter、Plutzky Jorge、Pradhan Aruna、Ridker Paul、Aguilar-Salinas Carlos、Al Rasadi Khalid、Yokote Koutaro、Zambon Alberto
  • Journal Title: Diabetes & Metabolic Syndrome: Clinical Research & Reviews Volume: 13 Issue: 4 Pages: 2723-2725
  • DOI: 10.1016/j.dsx.2019.05.034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential (2019)
  • Author(s): Fruchart Jean-Charles、Santos Raul D.Ponte-Negretti Carlos I、Pradhan Aruna、Ray Kausik K.、Reiner ?eljko、Ridker Paul M.、Ruscica Massimiliano、Sadikot Shaukat、Shimano Hitoshi. et al
  • Journal Title: Cardiovascular Diabetology Volume: 18 Issue: 1 Pages: 71-71
  • DOI: 10.1186/s12933-019-0864-7
  • NAID: 120007133397
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recommended configuration for personal health records by standardized data item sets for diabetes mellitus and associated chronic diseases: a report from a collaborative initiative by six Japanese associations (2019)
  • Author(s): Nakashima Naoki、Noda Mitsuhiko、Ueki Kohjiro、Koga Tatsuhiko、Hayashi Michio、Yamazaki Katsuya、Nakagami Tomoko、Ohara Makoto、Gochi Akira、Matsumura Yasushi、Kimura Michio、Ohe Kazuhiko、Kang Dongchon、Toya Yoshiyuki、Yamagata Kunihiro、Yokote Koutaro、Ikeda Shunya、Mitsutake Naohiro、Yamamoto Ryuichi、Tanizawa Yukio
  • Journal Title: Diabetology International Volume: 10 Issue: 2 Pages: 85-92
  • DOI: 10.1007/s13340-019-00389-7
  • Peer Reviewed
• [Journal Article] Comparing the effects of ipragliflozin versus metformin on visceral fat reduction and metabolic dysfunction in Japanese patients with type 2 diabetes treated with sitagliptin: A prospective, multicentre, open‐label, blinded‐endpoint, randomized controlled study (PRIME‐V study) (2019)
  • Author(s): Koshizaka Masaya、Ishikawa Ko、Ishibashi Ryoichi、Maezawa Yoshiro、Yokote Koutaro、On Behalf of the PRIME‐V Study Group
  • Journal Title: Diabetes, Obesity and Metabolism Volume: 21 Issue: 8 Pages: 1990-1995
  • DOI: 10.1111/dom.13750
  • Peer Reviewed
• [Journal Article] CXCL12-CXCR4 pathway activates brown adipocytes and induces insulin resistance in CXCR4-deficient mice under high-fat diet (2019)
  • Author(s): Kurita Kenichi、Ishikawa Ko、Takeda Kenji、Fujimoto Masanori、Ono Hiraku、Kumagai Jin、Inoue Hiromi、Yokoh Hidetaka、Yokote Koutaro
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 6165-6165
  • DOI: 10.1038/s41598-019-42127-8
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study (2019)
  • Author(s): Araki Eiichi、Yamashita Shizuya、Arai Hidenori、Yokote Koutaro、Satoh Jo、Inoguchi Toyoshi、Nakamura Jiro、Maegawa Hiroshi、Yoshioka Narihito、Tanizawa Yukio、Watada Hirotaka、Suganami Hideki、Ishibashi Shun
  • Journal Title: Diabetes, Obesity and Metabolism Volume: 21 Issue: 7 Pages: 1737-1744
  • DOI: 10.1111/dom.13686
  • Peer Reviewed / Open Access
• [Journal Article] Syringaresinol Reverses Age-Related Skin Atrophy by Suppressing FoxO3a-Mediated Matrix Metalloproteinase-2 Activation in Copper/Zinc Superoxide Dismutase-Deficient Mice (2019)
  • Author(s): Kim J, Toda T, Watanabe K, Shibuya S, Ozawa Y, Izuo N, Cho S, Seo DB, Yokote K, Shimizu T
  • Journal Title: J Invest Dermatol Volume: 139 Issue: 3 Pages: 648-655
  • DOI: 10.1016/j.jid.2018.10.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characteristic Clinical Features of Werner Syndrome with a Novel Compound Heterozygous WRN Mutation c.1720+1G>A Plus c.3139-1G>C (2019)
  • Author(s): Matsumoto N, Ohta Y, Deguchi K, Kishida M, Sato K, Shang J, Takemoto M, Hishikawa N, Yamashita T, Watanabe A, Yokote K, Takemoto M, Oshima J, Abe K
  • Journal Title: Intern Med Volume: 58 Pages: 1033-1036
  • NAID: 130007622212
  • Peer Reviewed / Open Access
• [Journal Article] Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study (2018)
  • Author(s): Itoh H, Komuro I, Takeuchi M, Akasaka T, Daida H, Yokote K
  • Journal Title: Diabetes Obes Metab Volume: - Issue: 4 Pages: 791-800
  • DOI: 10.1111/dom.13575
  • NAID: 120006601525
  • Peer Reviewed / Open Access
• [Journal Article] Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development (2018)
  • Author(s): Ide S, Finer G, Maezawa Y, Onay T, Souma T, Scott R, Ide K, Akimoto Y, Li C,Ye M, Zhao X, Baba Y, Minamizuka T, Jin J, Takemoto M, Yokote K, Quaggin SE
  • Journal Title: J Am Soc Nephrol Volume: 29 Issue: 12 Pages: 2795-2808
  • DOI: 10.1681/asn.2017121278
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Biallelic WRN Mutations in Newly Identified Japanese Werner Syndrome Patients (2018)
  • Author(s): Maezawa Y, Kato H, Takemoto M, Watanabe A, Koshizaka M, Ishikawa T, Sargolzaeiaval F, Kuzuya M, Wakabayashi H, Kusaka T, Yokote K, Oshima J
  • Journal Title: Mol Syndromol Volume: 9 Issue: 4 Pages: 214-218
  • DOI: 10.1159/000489055
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RECQ helicase disease and related progeroid syndromes: RECQ2018 meeting (2018)
  • Author(s): Oshima J, Kato H, Maezawa Y, Yokote K
  • Journal Title: Mech Ageing Dev Volume: 173 Pages: 80-83
  • DOI: 10.1016/j.mad.2018.05.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Physician-initiated clinical study of limb ulcers treated with a functional peptide, SR-0379: from discovery to a randomized, double-blind, placebo-controlled trial (2018)
  • Author(s): Nakagami H, Sugimoto K, Ishikawa T, Fujimoto T, Yamaoka T, Hayashi M, Kiyohara E, Ando H, Terabe Y, Takami Y, Yamamoto K, Takeya Y, Takemoto M, Koshizaka M, Ebihara T, Nakamura A, Nishikawa M, Yao XJ, Hanaoka H, Katayama I, Yokote K, Rakugi H
  • Journal Title: NPJ Aging Mech Dis Volume: 4 Issue: 1 Pages: 2-2
  • DOI: 10.1038/s41514-018-0021-7
  • Peer Reviewed / Open Access
• [Journal Article] N-3 polyunsaturated fatty acids improve lipoprotein particle size and concentration in Japanese patients with type 2 diabetes and hypertriglyceridemia:a pilot study (2018)
  • Author(s): Ide K, Koshizaka M, Tokuyama H, Tokuyama T, Ishikawa T, Maezawa Y, Takemoto M, Yokote K
  • Journal Title: Lipids Health Dis Volume: 17 Issue: 1 Pages: 51-51
  • DOI: 10.1186/s12944-018-0706-8
  • Peer Reviewed / Open Access
• [Journal Article] Apple procyanidins promote mitochondrial biogenesis and proteoglycan biosynthesis in chondrocytes. (2018)
  • Author(s): Masuda I, Koike M, Nakashima S, Mizutani Y, Ozawa Y, Watanabe K, Sawada Y, Sugiyama H, Sugimoto A, Nojiri H, Sashihara K, Yokote K, Shimizu T
  • Journal Title: Sci Rep. Volume: ８ Issue: 1 Pages: 7229-7229
  • DOI: 10.1038/s41598-018-25348-1
  • Peer Reviewed / Open Access
• [Journal Article] Immune-mediated acquired lecithin-cholesterol acyltransferase deficiency: A case report and literature review (2018)
  • Author(s): Ishibashi R, Takemoto M, Tsurutani Y, Kuroda M, Ogawa M, Wakabayashi H, Uesugi N, Nagata M, Imai N, Hattori A, Sakamoto K, Kitamoto T, Maezawa Y, Narita I, Hiroi S, Furuta A, Miida T, Yokote K
  • Journal Title: J Clin Lipidol Volume: 12 Issue: 4 Pages: 888-897
  • DOI: 10.1016/j.jacl.2018.05.002
  • Peer Reviewed
• [Journal Article] p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells. (2018)
  • Author(s): Nagano H, Hashimoto N, Nakayama A, Suzuki S, Miyabayashi Y, Yamato A, Higuchi S, Fujimoto M, Sakuma I, Beppu M, Yokoyama M, Suzuki Y, Sugano S, Ikeda K, Tatsuno I, Manabe I, Yokote K, Inoue S, Tanaka T.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 115 Issue: 33 Pages: 8370-8375
  • DOI: 10.1073/pnas.1804243115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human glomerular transcriptome of diabetic kidneys: Can the podocyte cytoskeleton be a therapeutic target? (2018)
  • Author(s): Maezawa Y, Yokote K
  • Journal Title: J Diabetes Investig Volume: 10 Issue: 2 Pages: 224-226
  • DOI: 10.1111/jdi.12951
  • Peer Reviewed / Open Access
• [Journal Article] Femoral osteoporosis is more common than lumbar osteoporosis in patients with Werner syndrome (2017)
  • Author(s): Mori Seijiro、Zhou Heying、Yamaga Masaya、Takemoto Minoru、Yokote Koutaro
  • Journal Title: Geriatr Gerontol Int. Volume: 17 Issue: 5 Pages: 854-856
  • DOI: 10.1111/ggi.12960
  • Peer Reviewed / Open Access
• [Journal Article] Werner syndrome: a model for sarcopenia due to accelerated aging (2017)
  • Author(s): Yamaga Masaya、Takemoto Minoru、Shoji Mayumi、Sakamoto Kenichi、Yamamoto Masashi、Ishikawa Takahiro、Koshizaka Masaya、Maezawa Yoshiro、Kobayashi Kazuki、Yokote Koutaro
  • Journal Title: Aging Volume: 9 Issue: 7 Pages: 1738-1744
  • DOI: 10.18632/aging.101265
  • Peer Reviewed / Open Access
• [Journal Article] Recent trends in WRN gene mutation patterns in individuals with Werner syndrome. (2017)
  • Author(s): Yamaga M, Takemoto M, Takada-Watanabe A, Koizumi N, Kitamoto T, Sakamoto K, Ishikawa T, Koshizaka M, Maezawa Y, Yokote K
  • Journal Title: J Am Geriatr Soc Volume: 印刷中 Issue: 8 Pages: 1853-1856
  • DOI: 10.1111/jgs.14906
  • Peer Reviewed / Open Access
• [Journal Article] The clinical characteristics of Asian patients with classical-type Hutchinson?Gilford progeria syndrome (2017)
  • Author(s): Sato-Kawano Nanae、Takemoto Minoru、Okabe Emiko、Yokote Koutaro、Matsuo Muneaki、Kosaki Rika、Ihara Kenji
  • Journal Title: J Hum Genet Volume: 62 Issue: 12 Pages: 1031-1035
  • DOI: 10.1038/jhg.2017.90
  • Peer Reviewed
• [Journal Article] Sitagliptin but not alpha glucosidase inhibitor reduced the serum soluble CD163, a marker for activated macrophage, in individuals with type 2 diabetes mellitus. (2017)
  • Author(s): Hattori A, Takemoto M, Tokuyama H, Koshizaka M, Yokote K.
  • Journal Title: Diabetes Res Clin Pract. Volume: 126 Pages: 138-143
  • DOI: 10.1016/j.diabres.2017.02.010
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of ipragliflozin and metformin for visceral fat reduction in patients with type 2 diabetes receiving treatment with dipeptidyl peptidase-4 inhibitors in Japan: a study protocol for a prospective, multicentre, blinded-endpoint phase IV randomised controlled trial (PRIME-V study) (2017)
  • Author(s): Koshizaka Masaya、Ishikawa Ko、Ishikawa Takahiro、Kobayashi Kazuki、Takemoto Minoru、Horikoshi Takuro、Shimofusa Ryota、Takahashi Sho、Nagashima Kengo、Sato Yasunori、Tatsuno Ichiro、Terano Takashi、Hashimoto Naotake、Kuribayashi Nobuichi、Uchida Daigaku、Yokote Koutaro
  • Journal Title: BMJ Open Volume: 7 Issue: 5 Pages: e015766-e015766
  • DOI: 10.1136/bmjopen-2016-015766
  • Peer Reviewed / Open Access
• [Journal Article] A toxic conformer of Aβ42 with a turn at 22-23 is a novel therapeutic target for Alzheimer’s disease (2017)
  • Author(s): Naotaka Izuo, Chihiro Kasahara, Kazuma Murakami, Toshiaki Kume, Masahiro Maeda, Kazuhiro Irie, Koutaro Yokote, Takahiko Shimizu
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 11811-11811
  • DOI: 10.1038/s41598-017-11671-6
  • NAID: 120006368174
  • Peer Reviewed / Open Access
• [Journal Article] Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction (2017)
  • Author(s): Wang H,Zhang X-M,Tomiyoshi G,Nakamura R,Shinmen N,Kuroda H,Kimura R,Mine S,Kamitsukasa I,Wada T,Aotsuka A,Yoshida Y,Kobayashi E,Matsutani T,Iwadate Y,Sugimoto K,Mori M,Uzawa A,Muto M,Kuwabara S,Takemoto M,Kobayashi K,Kawamura H,Ishibashi R,Yokote K,Ohno M,
  • Journal Title: Oncotarget Volume: 9 Issue: 5 Pages: 5600-5613
  • DOI: 10.18632/oncotarget.23789
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 座談会 脂質異常症治療のポイントと今後の展望～家族性高コレステロール血症を含めて～ (2017)
  • Author(s): 横手幸太郎、木下大輔、小倉正恒
  • Journal Title: 日本内科学会雑誌 Volume: 160 Pages: 742-754
  • Peer Reviewed
• [Journal Article] PCSK9阻害薬の臨床応用 (2017)
  • Author(s): 井出真太郎、前澤善朗、横手幸太郎
  • Journal Title: Diabetes Frontier Volume: 2 Pages: 139-146
  • Peer Reviewed
• [Journal Article] ウェルナー症候群の特徴と診療の実際 (2017)
  • Author(s): 越坂理也、横手幸太郎
  • Journal Title: 新薬と臨牀 Volume: 66 Pages: 96-102
  • Peer Reviewed
• [Presentation] 早老症から学ぶ糖尿病と動脈硬化 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第197回練馬区医師会学術部消化器懇話会
  • Invited
• [Presentation] 高齢2型糖尿病患者の薬物治療と包括的管理～最近のエビデンスをふまえて～ (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第36回日本臨床内科医会総会 ランチョンセミナーⅡ
  • Invited
• [Presentation] Novel approaches to overcome rare diseases: preadipocyte-based gene therapy and iPS cells from progeroid syndrome. (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第19回遺伝子・デリバリーシンポジウム
  • Invited
• [Presentation] 日本人におけるDPP-4阻害薬の次の一手を考える (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第62回日本糖尿病学会年次学術集会
  • Invited
• [Presentation] 早老症候群に合併する代謝異常 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第62回日本糖尿病学会年次学術集会 シンポジウム17
  • Invited
• [Presentation] Progeroid syndrome as a model of accelerated human aging. (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第62回日本糖尿病学会年次学術集会 シンポジウム23
  • Invited
• [Presentation] 動脈硬化予防のための脂質異常症治療Update (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第51回日本動脈硬化学会総会・学術集会 ランチョンセミナー1
  • Invited
• [Presentation] 動脈硬化リスクとしての高TG血症とSPPARMαの可能性 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第51回日本動脈硬化学会総会・学術集会 スポンサードシンポジウム3
  • Invited
• [Presentation] 最新エビデンスに基づく脂質管理のすすめ (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第70回日本老年医学会 関東甲信越地方会
  • Invited
• [Presentation] 2型糖尿病治療の新たな選択肢 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 2019 EASD Japan Symposium
  • Invited
• [Presentation] 動脈硬化の視点から血糖降下薬を考える (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第34回日本糖尿病合併症学会 シンポジウム1
  • Invited
• [Presentation] 高齢者糖尿病の薬物治療と包括的管理－インスリンの考え方を含めて― (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第34回日本糖尿病合併症学会・第25回日本糖尿病眼学会総会 共催イブニングセミナー2
  • Invited
• [Presentation] 早老症から学ぶ生活習慣病の治療 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 千葉県内科医会学術講演会
  • Invited
• [Presentation] 健康長寿社会と肥満 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第40回日本肥満学会 第37回日本肥満症治療学会 JASSO会長講演
  • Invited
• [Presentation] 肥満症に対する多施設共同減量介入研究（SLIM-TARGET研究）の展開 (2019)
  • Author(s): 横尾英孝、横手幸太郎、越坂理也、武田健治、前田祐香里、石川耕、小野啓、佐藤泰憲、浅原哲子、下村伊一郎、龍野一郎、津下一代、山内敏正、門脇孝
  • Organizer: 第40回日本肥満学会 第37回日本肥満症治療学会 シンポジウム4
• [Presentation] Change in body composition and improvement of glucose metabolism after bariatric surgery. (2019)
  • Author(s): Aiko Hayashi, Yoshiro Maezawa, Yukari Maeda, Koshizaka Masaya, Aya Kitahara, Hiraku Ono, Hideki Hayashi, Koutaro Yokote
  • Organizer: 第40回日本肥満学会 第37回日本肥満症治療学会 Japan Korea Taiwan (JKT) Joint Symposium 肥満治療の未来
• [Presentation] 早老症から学ぶ糖尿病：研究と診断の進歩 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 第39回内分泌セミナー特別講演会
  • Invited
• [Presentation] 早老症に立脚したヒト老化病態の解明とその制御への応用 (2019)
  • Author(s): 横手幸太郎
  • Organizer: AMED“老化メカニズムの解明・制御プロジェクト”第3回リトリートプログラム
• [Presentation] 早老症ウェルナー症候群の症例登録システムの構築・運営に基づくデータ集積とエビデンスの創生 (2019)
  • Author(s): 横手幸太郎
  • Organizer: 国立研究開発法人日本医療研究開発機構 2019年度合同成果報告会 難治性疾患実用化研究事業 免疫アレルギー疾患実用化研究事業 疾患克服への挑戦 2019
• [Presentation] Human model of accelerated aging and atherosclerosis (2018)
  • Author(s): Yokote K
  • Organizer: 18th International symposium on atherosclerosis
  • Int'l Joint Research
• [Presentation] Overview of clinical trials with a SPPARMα in patients with dyslipidaemia: Japanese and European experience (2018)
  • Author(s): Yokote K
  • Organizer: International Atherosclerosis Society Joint Symposium : The Selective Peroxisome Proliferator - Activated Receptor Alpha Modulator (SPPARMα) Concept
  • Int'l Joint Research
• [Presentation] Comparing the Effects of Ipragliflozin and Metformin on Visceral Fat Reduction in Patients with Type 2 Diabetes Inadequately Controlled with Sitagliptin - A Prospective, Multicenter, Blinded-Endpoint, Randomized Controlled Study in Japan (PRIME-V Study) (2018)
  • Author(s): Koshizaka M, Yokote K, Ishibashi R,Maezawa Y, Sakamoto K, Yokoh H, Onishi S, Kobayashi K, Tokuyama H, Ishikawa T, Shoji M, Ide S, Ide K, Baba Y, Horikoshi T, Shimofusa R, Takahashi S, Nagashima K, Sato Y, Takemoto M, On behalf of the PRIME-V study group
  • Organizer: the American Diabetes Association's 78th Scientific Sessions
  • Int'l Joint Research
• [Presentation] Comparison of ipragliflozin and metformin for visceral fat reduction in elderly patients with type 2 diabetes: a prospective, blinded-endpoint, randomised controlled study (2018)
  • Author(s): Koshizaka M, Yokote K, Ishikawa K, Ishibashi R, Yoko H, Sakamoto K, Ishikawa T, Maezawa Y, Takemoto M, PRIME-V Study Group Chiba University Hospital, Chiba Japan
  • Organizer: European Association for the Study of Diabetes 54th Annual Meeting
  • Int'l Joint Research
• [Presentation] ピオグリタゾンから安全にメトホルミンに切り替え得たWerner症候群の1例 (2018)
  • Author(s): 寺本直弥, 南塚拓也, 前田祐香里, 馬場雄介, 山本雅, 加藤尚也, 石川崇広, 越坂理也, 前澤善朗, 横手幸太郎
  • Organizer: 第115回日本内科学会総会・講演会
• [Presentation] 早老症ウェルナー症候群の全国疫学調査およびレジストリ構築によるエビデンスの創生 (2018)
  • Author(s): 越坂理也, 石川崇広, 加藤尚也, 前澤善朗, 竹本稔, 横手幸太郎
  • Organizer: 第60回日本老年医学会学術集会
• [Presentation] 細胞老化を認めたにも関わらず、難治性皮膚潰瘍を著明に改善し得たWerner症候群の1例 (2018)
  • Author(s): 木下大輔, 金子ひより, 加藤尚也, 石川崇広, 越坂理也, 前澤善朗, 緒方英之, 窪田吉孝, 三川信之, 横手幸太郎
  • Organizer: 日本老年医学会関東甲信越地方会第68回大会
• [Presentation] ヒトの老化促進病態としての早老症ウエルナー症候群：研究と診療の進歩 (2018)
  • Author(s): 横手幸太郎
  • Organizer: 第39回日本基礎老化学会シンポジウム 栄養・代謝シグナルと老化制御機構の接点
• [Presentation] (特別講演) 早老症から学ぶ糖尿病と動脈硬化 (2018)
  • Author(s): 横手幸太郎
  • Organizer: 第69回兵庫県糖尿病懇話会
• [Presentation] (特別講演) 早老症研究から学ぶ糖尿病治療 (2018)
  • Author(s): 横手幸太郎
  • Organizer: 第3回内分泌・糖尿病TUNE-UPセミナー
• [Presentation] (講演) 早老症に立脚したヒト老化病態の解明とその制御への応用 (2018)
  • Author(s): 横手幸太郎
  • Organizer: AMED老化メカニズムの解明・制御プロジェクト第二回リトリート
• [Presentation] (講演) 早老症から学ぶ老化と生活習慣病 (2018)
  • Author(s): 横手幸太郎
  • Organizer: 愛媛大学医学部附属病院先端医療創生センター主催セミナー
• [Presentation] (講演) 早老症ウェルナー症候群の診療と研究 (2018)
  • Author(s): 横手幸太郎
  • Organizer: 第51回ヒューマンサイエンス総合研究セミナー 老化のメカニズムを知り、加齢性疾患の新たな創薬の可能性を探る！
• [Presentation] 15.正常血糖クランプ法でインスリン抵抗性が確認されたウェルナー症候群の2例 (2018)
  • Author(s): 五十嵐活志, 前澤善朗, 金子ひより, 高崎敦史, 木下大輔, 石川崇広, 横尾英孝, 永野秀和, 越坂理也, 横手幸太郎
  • Organizer: 日本糖尿病学会第56回関東甲信越地方会
• [Presentation] 32.Werner Syndrome Research in Japan: For the Patient and Aging Scienece. (2018)
  • Author(s): 横手幸太郎
  • Organizer: International symposium on RECQ Helicases and Related Diseases 2018
• [Presentation] A case of Werner syndrome with isolatedocorticotropic hormone deficiency, Poster (2018)
  • Author(s): Yusuke Baba, Kana Ide, Kazuki Kobayashi, Yohsiro Maezawa, Minoru Takemoto, Tomoaki Tanaka, and Koutaro Yokote
  • Organizer: International symposium on RECQ Helicases and Related Diseases 2018
  • Int'l Joint Research
• [Presentation] 19.Werner Syndrome Research in Japan: for the Patient and Aging Science, 口頭 (2018)
  • Author(s): 横手幸太郎
  • Organizer: International Meeting on RECQ Helicases and Related Diseases 2018
  • Int'l Joint Research
• [Presentation] 高齢者糖尿病の薬物治療と包括的管理, 口頭 (2017)
  • Author(s): 横手幸太郎
  • Organizer: 第34回日本臨床内科医会総会
• [Presentation] ウェルナー症候群患者由来iPS細胞の間葉系幹細胞への分化誘導およびその老化表現型、口頭 (2017)
  • Author(s): 加藤尚也、前澤善朗、大内靖夫、石川崇広、越坂理也、岩間厚志、江藤浩之、横手幸太郎
  • Organizer: 第59回日本老年医学会学術集会
• [Remarks] ウェルナー症候群（ 千葉大学大学院医学研究院 内分泌代謝・血液・老年内科学）
  • URL: https://www.m.chiba-u.jp/dept/clin-cellbiol/werner/