Comprehensive multi-omics analysis for biological aging markers according to frailty model

• Project/Area Number: 21K17699
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Waseda University (2022); National Institutes of Biomedical Innovation, Health and Nutrition (2021)
• Principal Investigator: Watanabe Daiki 早稲田大学, スポーツ科学学術院, 助教 (90894501)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: フレイル / 疫学 / バイオマーカー / プロテオミクス / メタボロミクス / 生物学的老化 / マルチオミクス解析 / 傾向スコアマッチング

Outline of Research at the Start

フレイルはフィットの対義語として定義されており、暦年齢ではなく生物学的年齢（身体的予備能力）が重要である。本研究はフレイルの概念モデルに基づく予備能力に応じた4群を対象にする。フレイルは、表現型モデルを用いて定義する。これらの対象者は、年齢および性別をマッチングさせる。バイオマーカーは、血清サンプルを用いたプロテオミクスおよびメタボロミクスを実施する。本研究は年齢に依存しない生物学的老化との関連要因を明らかにし、フレイルの早期発見の有用な知見を得るであろう。

Outline of Final Research Achievements

Based on the data of middle-aged and older people, we matched age and gender based on a phenotype model for evaluating frailty and divided them into four groups according to their reserve ability: “fit,” “well,” “pre-frailty,” and “frailty.” classified. This makes it possible to search for biomarkers related to physical reserve ability that are not simply chronological age differences. Biomarkers were evaluated using blood samples. Proteomics detected 2059 proteins, with 44 proteins trending associated with degrees of frailty. On the other hand, in metabolomics, 192 types of metabolites were detected by target analysis, and about 50 known and unknown molecules showed a tendency relationship according to the degree of frailty.

Academic Significance and Societal Importance of the Research Achievements

世界中の多くの研究でフレイルの有無が高齢者の健康や寿命に影響を及ぼすことが示されたことに伴い、我が国では2020年4月より75歳以上の後期高齢者を対象に、フレイルの発症予防・重症化予防に着目した健診が開始された。従って、我々のデータは年齢に依存しない生物学的老化との関連要因を明らかにし、フレイルの早期発見の有用な知見を得るであろう。

Research Products

• [Journal Article] Dose-Response Relationships between Objectively Measured Daily Steps and Mortality among Frail and Non-frail Older Adults (2023)
  • Author(s): Watanabe Daiki、Yoshida Tsukasa、Watanabe Yuya、Yamada Yosuke、Miyachi Motohiko、Kimura Misaka
  • Journal Title: Medicine & Science in Sports & Exercise Volume: Publish Ahead of Print Issue: 6 Pages: 0-12
  • DOI: 10.1249/mss.0000000000003133
  • Peer Reviewed / Open Access
• [Journal Article] Association between excess mortality in depressive status and frailty among older adults: A population-based Kyoto-Kameoka prospective cohort study (2023)
  • Author(s): Watanabe Daiki、Yoshida Tsukasa、Yamada Yosuke、Watanabe Yuya、Yamagata Emi、Miyachi Motohiko、Fujiwara Yoshinori、Kimura Misaka
  • Journal Title: Archives of Gerontology and Geriatrics Volume: 110 Pages: 104990-104990
  • DOI: 10.1016/j.archger.2023.104990
  • Peer Reviewed / Open Access
• [Journal Article] Combined use of two frailty tools in predicting mortality in older adults (2022)
  • Author(s): Watanabe Daiki、Yoshida Tsukasa、Yamada Yosuke、Watanabe Yuya、Yamada Minoru、Fujita Hiroyuki、Miyachi Motohiko、Arai Hidenori、Kimura Misaka
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 15042-15042
  • DOI: 10.1038/s41598-022-19148-x
• [Journal Article] Validation of the Kihon Checklist and the frailty screening index for frailty defined by the phenotype model in older Japanese adults (2022)
  • Author(s): Watanabe Daiki、Yoshida Tsukasa、Watanabe Yuya、Yamada Yosuke、Miyachi Motohiko、Kimura Misaka
  • Journal Title: BMC Geriatrics Volume: 22 Issue: 1 Pages: 478-478
  • DOI: 10.1186/s12877-022-03177-2
• [Journal Article] Doubly labelled water‐calibrated energy intake associations with mortality risk among older adults (2022)
  • Author(s): Watanabe Daiki、Yoshida Tsukasa、Watanabe Yuya、Kimura Misaka、Yamada Yosuke、Kyoto?Kameoka Study Group
  • Journal Title: Journal of Cachexia, Sarcopenia and Muscle Volume: 14 Issue: 1 Pages: 214-225
  • DOI: 10.1002/jcsm.13122
• [Journal Article] Diet quality and physical or comprehensive frailty among older adults (2022)
  • Author(s): Watanabe Daiki、Kurotani Kayo、Yoshida Tsukasa、Nanri Hinako、Watanabe Yuya、Date Heiwa、Itoi Aya、Goto Chiho、Ishikawa-Takata Kazuko、Kimura Misaka、Miyachi Motohiko、Yamada Yosuke、Kyoto-Kameoka Study Group
  • Journal Title: European Journal of Nutrition Volume: none Issue: 5 Pages: 2451-2462
  • DOI: 10.1007/s00394-022-02819-w
  • Peer Reviewed / Open Access
• [Journal Article] Adequate Protein Intake on Comprehensive Frailty in Older Adults: Kyoto-Kameoka Study (2022)
  • Author(s): Nanri Hinako、Watanabe D.、Yoshida T.、Yoshimura E.、Okabe Y.、Ono M.、Koizumi T.、Kobayashi H.、Fujita H.、Kimura M.、Yamada Y.、for the Kyoto-Kameoka Study Group
  • Journal Title: The journal of nutrition, health & aging Volume: 26 Issue: 2 Pages: 161-168
  • DOI: 10.1007/s12603-022-1740-9
  • Peer Reviewed
• [Journal Article] Doubly labelled water-calibration approach attenuates the underestimation of energy intake calculated from self-reported dietary assessment data in Japanese older adults (2021)
  • Author(s): Watanabe Daiki、Yoshida Tsukasa、Yoshimura Eiichi、Nanri Hinako、Goto Chiho、Ishikawa-Takata Kazuko、Ebine Naoyuki、Fujita Hiroyuki、Kimura Misaka、Yamada Yosuke、Kyoto-Kameoka Study Group
  • Journal Title: Public Health Nutrition Volume: none Issue: 7 Pages: 1893-1903
  • DOI: 10.1017/s1368980021003785
  • Peer Reviewed / Open Access
• [Journal Article] Adherence to the food-based Japanese dietary guidelines and prevalence of poor oral health-related quality of life among older Japanese adults in the Kyoto-Kameoka study. (2021)
  • Author(s): Watanabe D, Kurotani K, Yoshida T, Nanri H, Watanabe Y, Date H, Itoi A, Goto C, Ishikawa-Takata K, Kikutani T, Yoshida M, Fujita H, Yamada Y, Kimura M; Kyoto-Kameoka Study Group.
  • Journal Title: Br J Nutr Volume: 27 Issue: 3 Pages: 1-10
  • DOI: 10.1017/s0007114521003329
  • Peer Reviewed / Open Access
• [Presentation] Doubly labeled water-calibrated energy intake associations with mortality risk among older adults from the Kyoto-Kameoka Study (2022)
  • Author(s): Daiki Watanabe, Tsukasa Yoshida, Yuya Watanabe, Misaka Kimura, Yosuke Yamada, Kyoto-Kameoka Study Group
  • Organizer: Recent Advances and Controversies in the Measurement of Energy Metabolism
  • Int'l Joint Research
• [Presentation] 高齢者における校正済みたんぱく質摂取量と包括的フレイルとの関連：Kyoto-Kameoka Study (2021)
  • Author(s): 南里妃名子 , 渡邉大輝 , 吉田司 , 吉村英一 , 岡辺有紀 , 小野美保 , 小泉友範 , 小林久峰 , 藤田裕之 , 木村みさか , 山田陽介
  • Organizer: 第8回日本サルコペニア・フレイル学会大会
• [Presentation] 中高齢者における指輪っかテストでスクリーニングされたサルコペニアに関連する要因 (2021)
  • Author(s): 渡邉大輝 , 吉田司 , 中潟崇 , 澤田奈緒美 , 山田陽介 , 黒谷佳代 , 岡林恵 , 島田秀和 , 瀧本秀美 , 西信雄 , 阿部圭一 , 宮地元彦
  • Organizer: 第80回日本公衆衛生学会総会