Deciphering aging mechanism

• Project/Area Number: 16K15415
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Keio University
• Principal Investigator: Yuasa Shinsuke 慶應義塾大学, 医学部(信濃町), 講師 (90398628)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 老化 / 細胞 / 実験モデル / ヒト / モデル

Outline of Final Research Achievements

Aging is the basis of various human diseases. In order to develop the medical approach to control aging, it is necessary to understand the molecular basis of aging. Aging research is conducted by cellular model in vitro, short-lived experimental organisms such as nematodes, genetically modified mice, long-term intervention studies using large animals such as monkeys, genetic analysis studies on hereditary aging syndrome, and iPS cells derived from patients with aging syndrome. All experimental models have strengths and weaknesses, and have been studied complementarily. In this study, we used a variety of models to search for aging mechanisms.

Academic Significance and Societal Importance of the Research Achievements

本研究により、老化の進展に関わる分子を特定している。同分子に介入することにより、老化モデルにおける老化の制御に成功している。今後は、さらなる老化モデルでの検証を行い、詳細な分子機序の探索を継続する。将来は、老化を制御する薬剤の開発へ役立つ可能性がある。

Research Products

• [Journal Article] Automated Deep Learning-Based System to Identify Endothelial Cells Derived from Induced Pluripotent Stem Cells. (2019)
  • Author(s): Kusumoto D, Lachmann M, Kunihiro T, Yuasa S, Kishino Y, Kimura M, Katsuki T, Itoh S, Seki T, Fukuda K
  • Journal Title: Circ Res. Volume: 10(6) Pages: 1687-1695
  • DOI: 10.1161/circresaha.119.314678
  • Peer Reviewed
• [Journal Article] A tale of two sisters with hypertrophic cardiomyopathy and recurrent embolism: When is the optimal timing of the intervention for left atrial appendage? (2019)
  • Author(s): Kimura Mai、Kohno Takashi、Makino Shinji、Okuda Shigeo、Nawata Kan、Yanagisawa Ryo、Kojima Hidenori、Nishiyama Takahiko、Aizawa Yoshiyasu、Yuasa Shinsuke、Murata Mitsushige、Maekawa Yuichiro、Okamoto Kazuma、Shimizu Hideyuki、Fukuda Keiichi
  • Journal Title: Heart Lung. Volume: 48 Pages: 198-200
  • DOI: 10.1016/j.hrtlng.2018.08.010
  • Peer Reviewed / Open Access
• [Journal Article] Shortening Hospital Stay Is Feasible and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty (2019)
  • Author(s): Kimura Mai、Kohno Takashi、Kawakami Takashi、Kataoka Masaharu、Hiraide Takahiro、Moriyama Hidenori、Isobe Sarasa、Tsugu Toshimitsu、Itabashi Yuji、Murata Mitsushige、Yuasa Shinsuke、Fukuda Keiichi
  • Journal Title: Can J Cardiol. Volume: 35 Pages: 193-198
  • DOI: 10.1016/j.cjca.2018.12.001
  • Peer Reviewed
• [Journal Article] Selective modulation of local linkages between active transcription and oxidative demethylation activity shapes cardiomyocyte-specific gene-body epigenetic status in mice. (2018)
  • Author(s): Oda M, Wakabayashi S, Ari Wijetunga N, Yuasa S, Enomoto H, Kaneda R, Yoon SH, Mittal N, Jing Q, Suzuki M, Greally JM, Fukuda K, Makino S
  • Journal Title: BMC Genomics. Volume: 19 Pages: 1-15
  • DOI: 10.1186/s12864-018-4752-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic significance of repeated brain natriuretic peptide measurements after percutaneous transluminal septal myocardial ablation in patients with drug-refractory hypertrophic obstructive cardiomyopathy. (2018)
  • Author(s): Akita K, Tsuruta H, Yuasa S, Murata M, Fukuda K, Maekawa Y
  • Journal Title: Open Heart. Volume: 5(1)
  • DOI: 10.1136/openhrt-2018-000786
  • Peer Reviewed / Open Access
• [Journal Article] Improvement in the electrocardiograms associated with right ventricular hypertrophy after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension (2018)
  • Author(s): Nishiyama Takahiko、Takatsuki Seiji、Kawakami Takashi、Katsumata Yoshinori、Kimura Takehiro、Kataoka Masaharu、Tsuruta Hikaru、Itabashi Yuji、Murata Mitsushige、Yuasa Shinsuke、Aizawa Yoshiyasu、Fukuda Keiichi
  • Journal Title: Int J Cardiol Heart Vasc. Volume: 19 Pages: 75-82
  • DOI: 10.1016/j.ijcha.2018.05.003
  • Peer Reviewed / Open Access
• [Journal Article] Excessive Daytime Sleepiness Is Associated With Depression Scores, But Not With Sleep-Disordered Breathing in Patients With Cardiovascular Diseases (2018)
  • Author(s): Ohashi M, Kohno T, Kohsaka S, Fukuoka R, Hayashida K, Yuasa S, Sano M, Takatsuki S, Fukuda K.
  • Journal Title: Circ J Volume: 82(8) Issue: 8 Pages: 2175-2183
  • DOI: 10.1253/circj.cj-17-1395 10.1253/circj.CJ-17-1395
  • NAID: 130007419855
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Impact of catheter-induced iatrogenic coronary artery dissection with or without postprocedural flow impairment: A report from a Japanese multicenter percutaneous coronary intervention registry. (2018)
  • Author(s): Hiraide T, Sawano M, Shiraishi Y, Ueda I, Numasawa Y, Noma S, Negishi K, Ohki T, Yuasa S, Hayashida K, Miyata H, Fukuda K, Kohsaka S.
  • Journal Title: PLOS ONE Volume: 13(9)
  • DOI: 10.1371/journal.pone.0204333
  • Peer Reviewed / Open Access
• [Journal Article] Stroke After Percutaneous Coronary Intervention in the Era of Transradial Intervention. (2018)
  • Author(s): Shoji S, Kohsaka S, Kumamaru H, Sawano M, Shiraishi Y, Ueda I, Noma S, Suzuki M, Numasawa Y, Hayashida K, Yuasa S, Miyata H, Fukuda K.
  • Journal Title: Circ Cardiovasc Interv. Volume: 11(12)
  • DOI: 10.1161/circinterventions.118.006761
  • Peer Reviewed
• [Journal Article] Patient confidence regarding secondary lifestyle modification and knowledge of 'heart attack' symptoms following percutaneous revascularisation in Japan: a cross-sectional study. (2018)
  • Author(s): Kitakata H, Kohno T, Kohsaka S, Fujino J, Nakano N, Fukuoka R, Yuasa S, Maekawa Y, Fukuda K.
  • Journal Title: BMJ Open. Volume: 8(3)
  • DOI: 10.1136/bmjopen-2017-019119
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous Occlusion of Patent Ductus Arteriosus for an Elderly Patient With Refractory Congestive Heart Failure. (2018)
  • Author(s): Shoji S, Kanazawa H, Yanagisawa R, Tanaka M, Fukuoka R, Akita K, Kimura M, Arai T, Kawakami T, Hayashida K, Yuasa S, Tsuruta H, Itabashi Y, Murata M, Nishiyama T, Kohno T, Maekawa Y, Fukuda K.
  • Journal Title: Circ Heart Fail. Volume: 2
  • DOI: 10.1161/circheartfailure.117.004764
  • Peer Reviewed
• [Journal Article] Characteristics and in-hospital outcomes in young patients presenting with acute coronary syndrome treated by percutaneous coronary intervention. (2018)
  • Author(s): Hirota Y, Sawano M, Numasawa Y, Ueda I, Noma S, Suzuki M, Hayashida K, Yuasa S, Maekawa Y, Kohsaka S, Fukuda K.
  • Journal Title: Cardiovasc Interv Ther. Volume: 33(2) Pages: 154-162
  • DOI: 10.1007/s12928-017-0471-z
  • NAID: 40021531353
  • Peer Reviewed
• [Journal Article] Predictors of high cost after percutaneous coronary intervention: A review from Japanese multicenter registry overviewing the influence of procedural complications. (2017)
  • Author(s): Inohara T, Numasawa Y, Higashi T, Ueda I, Suzuki M, Hayashida K, Yuasa S, Maekawa Y, Fukuda K, Kohsaka S.
  • Journal Title: Am Heart J. Volume: 194 Pages: 61-72
  • DOI: 10.1016/j.ahj.2017.08.008
  • Peer Reviewed
• [Journal Article] Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes. (2017)
  • Author(s): Kuroda Y, Yuasa S, Watanabe Y, Ito S, Egashira T, ・・・Horie M, Kamiya K, Fukuda K.
  • Journal Title: Biochemistry and biophysics reports Volume: 9 Pages: 245-256
  • DOI: 10.1016/j.bbrep.2017.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells. (2017)
  • Author(s): Saito Y, Kunitomi A, Seki T, Tohyama S, Kusumoto D, Takei M, Kashimura S, Hashimoto H, Yozu G, Motoda C, Shimojima M, Egashira T, Oda M, Fukuda K, Yuasa S.
  • Journal Title: FEBS Lett. Volume: 591(18) Pages: 2879-2889
  • DOI: 10.1002/1873-3468.12791
  • Peer Reviewed
• [Journal Article] Barriers Associated With Door-to-Balloon Delay in Contemporary Japanese Practice (2017)
  • Author(s): Ikemura N, Sawano M, Shiraishi Y, Ueda I, Miyata H, Numasawa Y, Noma S, Suzuki M, Momiyama Y, Inohara T, Hayashida K, Yuasa S, Maekawa Y, Fukuda K, Kohsaka S.
  • Journal Title: Circ J Volume: Epub ahead of print Issue: 6 Pages: 815-822
  • DOI: 10.1253/circj.cj-16-0905 10.1253/circj.CJ-16-0905
  • NAID: 130005679702
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient. (2017)
  • Author(s): Shimojima M, Yuasa S, Motoda C, Yozu G, Nagai T, Ito S, Lachmann M, Kashimura S, Takei M, Kusumoto D, Kunitomi A, Hayashiji N, Seki T, Tohyama S, Hashimoto H, Kodaira M, Egashira T, Hayashi K, Nakanishi C, Sakata K, Yamagishi M, Fukuda K.
  • Journal Title: Sci Rep. Volume: 7 Pages: 44312-44312
  • DOI: 10.1038/srep44312
  • NAID: 120006325351
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nocturnal intermittent hypoxia and short sleep duration are independently associated with elevated C-reactive protein levels in patients with coronary artery disease. (2017)
  • Author(s): Fukuoka R, Kohno T, Kohsaka S, Yanagisawa R, Kawakami T, Hayashida K, Kanazawa H, Yuasa S, Maekawa Y, Sano M, Fukuda K.
  • Journal Title: Sleep Med. Volume: 29 Pages: 29-34
  • DOI: 10.1016/j.sleep.2016.09.012
  • Peer Reviewed
• [Journal Article] An RyR2 mutation found in a family with a short-coupled variant of torsade de pointes. (2017)
  • Author(s): Kimura M, Fujisawa T, Aizawa Y, Matsuhashi N, Ito S, Nakajima K, Kashimura S, Kunitomi A, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Yuasa S, Takatsuki S, Kosaki K, Fukuda K.
  • Journal Title: Int J Cardiol. Volume: 227 Pages: 367-369
  • DOI: 10.1016/j.ijcard.2016.11.052
  • Peer Reviewed
• [Journal Article] Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles (2016)
  • Author(s): Kushiyama Y, Honjo H, Niwa R, Takanari H, Yamazaki M, Takemoto Y, Sakuma I, Kodama I, Kamiya K
  • Journal Title: Scientific Reports Volume: 311 Pages: 34198-34198
  • DOI: 10.1038/srep34198
  • NAID: 120005946586
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Significant reduction of left atrial volume concomitant with clinical improvement after percutaneous transluminal septal myocardial ablation for drug-refractory hypertrophic obstructive cardiomyopathy, and its precise detection with multidetector CT (2016)
  • Author(s): Maekawa Y, Akita K, Tsuruta H, Yamada Y,Hayashida K, Yuasa S, Murata M, Jinzaki M, Fukuda K
  • Journal Title: Open Heart. Volume: 3 Pages: 1-8
  • DOI: 10.1136/openhrt-2015-000359
  • Peer Reviewed / Open Access
• [Journal Article] H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells (2016)
  • Author(s): Kunitomi A, Yuasa S, Sugiyama F, Saito Y, Seki T, Kusumoto D, Kashimura S, Takei M, Tohyama S, Hashimoto H, Egashira T, Tanimoto Y, Mizuno S, Tanaka S, Okuno H, Yamazawa K, Watanabe H, Oda M, Kaneda R, Matsuzaki Y, Nagai T, Okano H, Yagami K, Tanaka M, Fukuda K.
  • Journal Title: Stem Cell Reports. Volume: 6 Pages: 825-33
  • DOI: 10.1016/j.stemcr.2016.04.015
  • NAID: 120007135348
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Intensive statin therapy stabilizes C-reactive protein, but not chemokine in stable coronary artery disease treated with an everolimus-eluting stent (2016)
  • Author(s): Sukegawa H., Abe, T. et al.
  • Journal Title: Coron Artery Dis Volume: 27 Pages: 405-11
  • DOI: 10.1097/mca.0000000000000375
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells. (2016)
  • Author(s): Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R, Kanazawa H, Seki T, Nakajima K, Kishino Y, Okada M, Hirano A, Kuroda T, Yasuda S, Sato Y, Yuasa S, Sano M, Suematsu M, Fukuda K.
  • Journal Title: Cell Metab. Volume: 23 Pages: 663-674
  • DOI: 10.1016/j.cmet.2016.03.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Arrhythmogenic disease modeling using iPS cells (2018)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 1st JCS Council Forum on Basic CardioVascular Research
  • Invited
• [Presentation] iPS細胞を用いた心不全の診断 (2017)
  • Author(s): 湯浅慎介
  • Organizer: 第２１回 日本心不全学会
  • Invited
• [Presentation] Cardiac Arrhythmia Modeling by Induced Pluripotent Stem Cells. (2017)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session In Conjunction with the Annual Meeting of the Japanese Heart Rhythm Society
  • Invited
• [Presentation] Disease modeling by iPS cells (2017)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session In Conjunction with the Annual Meeting of the Japanese Heart Rhythm Society
  • Invited
• [Presentation] iPS細胞を用いた循環器疾患の病態解明. (2017)
  • Author(s): 湯浅慎介
  • Organizer: 第38回 日本炎症・再生医学会
  • Invited
• [Presentation] iPS細胞を用いた心筋症の病態解明. (2017)
  • Author(s): 湯浅慎介
  • Organizer: 第3回 日本心筋症研究会
  • Invited