Exploratory research to find the healthy aging factor in Kyotango area and Multifactorial AI Analysis collaborating with Hisayama Study andthe Iwaki Health Promotion Project

• Project/Area Number: 19H03567
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Matoba Satoaki 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10305576)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: aging / senescense / atherosclerosis / endotheial function / hearthy aging / 長寿 / 老化 / 血管機能 / 百寿者 / エネルギー代謝 / 健康長寿 / 平均寿命 / 動脈硬化 / 健康寿命 / ＡＩ解析 / 血管老化 / 心筋エネルギー代謝 / 骨格筋代謝

Outline of Research at the Start

高齢化社会の急務課題は、いかに健康に人生を全うするかを解明することである。これまで、久山町研究にて日本人の死因は克明に研究され、弘前大学岩木町研究では、青森県の短命県返上を目指した2000項目に及ぶコホート研究が実施されているが、その2大コホート研究と連携し、同じ方法と健診項目を京都大学奥野研究室にてAIを利用することで、腸内細菌や遺伝情報、生活身体情報を含め多項目多角的解析を行う。京都府立医科大学の臨床全科が参加し、15年間追跡し、死因も検討することでコホート研究を行う。また、基礎研究・臨床研究のこれまでの研究と遺伝子研究を融合し、老化予防の機序解析も行い、健康長寿の因子を科学的に解明する。

Outline of Final Research Achievements

In the Kyotango area, the number of centenarians is about 2.7 times of the national average. In this study, we collected and accumulated health and medical data on about 2,000 factors from residents of Kyotango aged 65 and over.
As of March 2023, 950 health checkup data are analyzed, and AI analysis is currently being used to write a paper. We have published papers on aging, arteriosclerosis, and inflammation. We discovered that one amino acid in the blood is involved in maintenance of lifespan and exercise capacity, applied for a patent, and is currently continuing detailed analysis.

Academic Significance and Societal Importance of the Research Achievements

京丹後地域と京都市の腸内細菌検査での比較研究では、京丹後地域においてプロテオバクテリア門が少なくいこと、大腸がんの罹患率が低い事を報告しているが、（J Clin Biochem Nutr. 2019 Sep;65(2):125-131.）。他にも多くの長寿に関係する因子を解析することで、今後人類が直面する高齢化社会において健康を維持する方法をみつけることができる。また、同じ健診項目で検討している青森県岩木町と京丹後地域の研究結果比較から両地域の行動パターンや、検査値の相違を検討し、健康長寿の医学的メカニズムを解明し、疾病の予防及び健康の保持・増進を広く社会に普及させることができる。

Research Products

• [Journal Article] Repeated Social Defeat Enhances CaCl2-Induced Abdominal Aortic Aneurysm Expansion by Inhibiting the Early Fibrotic Response via the MAPK-MKP-1 Pathway. (2022)
  • Author(s): Kubota H, Yamada H, Sugimoto T, Wada N, Motoyama S, Saburi M, Miyawaki D, Wakana N, Kami D, Ogata T, Ibi M, Matoba S.
  • Journal Title: Cells Volume: 11 Issue: 4 Pages: 732-732
  • DOI: 10.3390/cells11040732
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Requirement of Cavin-2 for the expression and stability of IRβ in adequate adipocyte differentiation. (2022)
  • Author(s): Higuchi Y, Ogata T, Nakanishi N, Nishi M, Sakamoto A, Tsuji Y, Tomita S, Matoba S.
  • Journal Title: Mol Metab. Volume: 55 Pages: 101416101416-101416101416
  • Peer Reviewed
• [Journal Article] Repeated Social Defeat Exaggerates Fibrin-Rich Clot Formation by Enhancing Neutrophil Extracellular Trap Formation via Platelet-Neutrophil Interactions. (2021)
  • Author(s): Sugimoto T, Yamada H, Wada N, Motoyama S, Saburi M, Kubota H, Miyawaki D, Wakana N, Kami D, Ogata T, Ibi M, Matoba S.
  • Journal Title: cells Volume: 10 Issue: 12 Pages: 3344-3344
  • DOI: 10.3390/cells10123344
  • Peer Reviewed / Open Access
• [Journal Article] Energy‐sparing by 2‐methyl‐2‐thiazoline protects heart from ischaemia/reperfusion injury (2021)
  • Author(s): Nishi Masahiro、Ogata Takehiro、Kobayakawa Ko、Kobayakawa Reiko、Matsuo Tomohiko、Cannistraci Carlo Vittorio、Tomita Shinya、Taminishi Shunta、Suga Takaomi、Kitani Tomoya、Higuchi Yusuke、Sakamoto Akira、Tsuji Yumika、Soga Tomoyoshi、Matoba Satoaki
  • Journal Title: ESC Heart Failure Volume: 9 Issue: 1 Pages: 428-441
  • DOI: 10.1002/ehf2.13732
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Orotic acid protects pancreatic β cell by p53 inactivation in diabetic mouse model. (2021)
  • Author(s): Fushimura Y, Hoshino A, Furukawa S, Nakagawa T, Hino T, Taminishi S, Minami Y, Urata R, Iwai-Kanai E, Matoba S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 31 Pages: 195-199
  • DOI: 10.1016/j.bbrc.2021.10.060
  • Peer Reviewed / Open Access
• [Journal Article] Cellular senescence promotes endothelial activation through epigenetic alteration, and consequently accelerates atherosclerosis (2021)
  • Author(s): Honda S, Ikeda K, Urata R, Yamazaki E, Emoto N, Matoba S
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 14608-14608
  • DOI: 10.1038/s41598-021-94097-5
  • Peer Reviewed / Open Access
• [Journal Article] TIGAR reduces smooth muscle cell autophagy to prevent pulmonary hypertension (2020)
  • Author(s): Yamanaka R, Hoshino A, Fukai K, Urata R, Minami Y, Honda S, Fushimura Y, Hato D, Iwai-Kanai E, Matoba S.
  • Journal Title: Am J Physiol Heart Circ Physiol . Volume: 319 Issue: 5 Pages: H1087-H1096
  • DOI: 10.1152/ajpheart.00314.2020
  • Peer Reviewed
• [Journal Article] Social stress increases vulnerability to high-fat diet-induced insulin resistance by enhancing neutrophil elastase activity in adipose tissue. (2020)
  • Author(s): Motoyama S, Yamada H, Yamamoto K, Wakana N, Kikai M, Wada N, Saburi M, Sugimoto T, Kubota H, Miyawaki D, Kami D, Ogata T, Ibi M, Yabe-Nishimura C and Matoba S.
  • Journal Title: Cells Volume: 9 Issue: 4 Pages: 996-996
  • DOI: 10.3390/cells9040996
  • Peer Reviewed / Open Access
• [Journal Article] Maternal high-fat diet exaggerates diet-induced insulin resistance in adult offspring by enhancing inflammasome activation through noncanonical pathway of caspase-11 (2020)
  • Author(s): Wada N, Yamada H, Motoyama S, Saburi M, Sugimoto T, Kubota H, Miyawaki D, Wakana N, Kami D, Ogata T, Matoba S.
  • Journal Title: Mol Metab Volume: 37 Pages: 100988-100988
  • DOI: 10.1016/j.molmet.2020.100988
  • Peer Reviewed / Open Access
• [Journal Article] TAT‐dextran?mediated mitochondrial transfer enhances recovery from models of reperfusion injury in cultured cardiomyocytes (2020)
  • Author(s): Maeda Hideki、Kami Daisuke、Maeda Ryotaro、Murata Yuki、Jo Jun‐ichiro、Kitani Tomoya、Tabata Yasuhiko、Matoba Satoaki、Gojo Satoshi
  • Journal Title: Journal of Cellular and Molecular Medicine Volume: 24 Issue: 9 Pages: 5007-5020
  • DOI: 10.1111/jcmm.15120
  • NAID: 120006949377
  • Peer Reviewed / Open Access
• [Journal Article] Endothelial progeria induces adipose tissue senescence and impairs insulin sensitivity through senescence associated secretory phenotype. (2020)
  • Author(s): Barinda AJ, Ikeda K, Nugroho DB, Wardhana DA, Sasaki N, Honda S, Urata R, Matoba S, Hirata K, Emoto N.
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 481-481
  • DOI: 10.1038/s41467-020-14387-w
  • Peer Reviewed / Open Access
• [Journal Article] Gut microbiota differences in elderly subjects between rural city Kyotango and urban city Kyoto: an age-gender-matched study (2019)
  • Author(s): Naito Y, Takagi T, Inoue R, Kashiwagi S, Mizushima K, Tsuchiya S, Itoh Y, Okuda K, Tsujimoto Y, Adachi A, Maruyama N, Oda Y, Matoba S.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 65 Issue: 2 Pages: 125-131
  • DOI: 10.3164/jcbn.19-26
  • NAID: 130007700214
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access