IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59964-z.html
   My bibliography  Save this article

Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk

Author

Listed:
  • Filippos Anagnostakis

    (Columbia University)

  • Sarah Ko

    (Columbia University)

  • Mehrshad Saadatinia

    (Columbia University)

  • Jingyue Wang

    (Columbia University)

  • Christos Davatzikos

    (University of Pennsylvania)

  • Junhao Wen

    (Columbia University
    Columbia University
    New York Genome Center (NYGC)
    Columbia University)

Abstract

Multi-organ biological aging clocks across different organ systems have been shown to predict human disease and mortality. Here, we extend this multi-organ framework to plasma metabolomics, developing five organ-specific metabolome-based biological age gaps (MetBAGs) using 107 plasma non-derivatized metabolites from 274,247 UK Biobank participants. Our age prediction models achieve a mean absolute error of approximately 6 years (0.25

Suggested Citation

  • Filippos Anagnostakis & Sarah Ko & Mehrshad Saadatinia & Jingyue Wang & Christos Davatzikos & Junhao Wen, 2025. "Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59964-z
    DOI: 10.1038/s41467-025-59964-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59964-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59964-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Celeste McCracken & Zahra Raisi-Estabragh & Michele Veldsman & Betty Raman & Andrea Dennis & Masud Husain & Thomas E. Nichols & Steffen E. Petersen & Stefan Neubauer, 2022. "Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Tian Ge & Chia-Yen Chen & Yang Ni & Yen-Chen Anne Feng & Jordan W. Smoller, 2019. "Polygenic prediction via Bayesian regression and continuous shrinkage priors," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Minna K. Karjalainen & Savita Karthikeyan & Clare Oliver-Williams & Eeva Sliz & Elias Allara & Wing Tung Fung & Praveen Surendran & Weihua Zhang & Pekka Jousilahti & Kati Kristiansson & Veikko Salomaa, 2024. "Genome-wide characterization of circulating metabolic biomarkers," Nature, Nature, vol. 628(8006), pages 130-138, April.
    4. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    5. Usman A. Tahir & Daniel H. Katz & Julian Avila-Pachecho & Alexander G. Bick & Akhil Pampana & Jeremy M. Robbins & Zhi Yu & Zsu-Zsu Chen & Mark D. Benson & Daniel E. Cruz & Debby Ngo & Shuliang Deng & , 2022. "Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Fenglei Wang & Anne-Julie Tessier & Liming Liang & Clemens Wittenbecher & Danielle E. Haslam & Gonzalo Fernández-Duval & A. Heather Eliassen & Kathryn M. Rexrode & Deirdre K. Tobias & Jun Li & Oana Ze, 2023. "Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    7. Susan Cheng & Martin G. Larson & Elizabeth L. McCabe & Joanne M. Murabito & Eugene P. Rhee & Jennifer E. Ho & Paul F. Jacques & Anahita Ghorbani & Martin Magnusson & Amanda L. Souza & Amy A. Deik & Ke, 2015. "Distinct metabolomic signatures are associated with longevity in humans," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    8. Junhao Wen & Bingxin Zhao & Zhijian Yang & Guray Erus & Ioanna Skampardoni & Elizabeth Mamourian & Yuhan Cui & Gyujoon Hwang & Jingxuan Bao & Aleix Boquet-Pujadas & Zhen Zhou & Yogasudha Veturi & Mary, 2024. "The genetic architecture of multimodal human brain age," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Benjamin B. Sun & Joshua Chiou & Matthew Traylor & Christian Benner & Yi-Hsiang Hsu & Tom G. Richardson & Praveen Surendran & Anubha Mahajan & Chloe Robins & Steven G. Vasquez-Grinnell & Liping Hou & , 2023. "Plasma proteomic associations with genetics and health in the UK Biobank," Nature, Nature, vol. 622(7982), pages 329-338, October.
    10. Susan Cheng & Martin G. Larson & Elizabeth L. McCabe & Joanne M. Murabito & Eugene P. Rhee & Jennifer E. Ho & Paul F. Jacques & Anahita Ghorbani & Martin Magnusson & Amanda L. Souza & Amy A. Deik & Ke, 2015. "Erratum: Distinct metabolomic signatures are associated with longevity in humans," Nature Communications, Nature, vol. 6(1), pages 1-1, November.
    11. Jian Zeng & Angli Xue & Longda Jiang & Luke R. Lloyd-Jones & Yang Wu & Huanwei Wang & Zhili Zheng & Loic Yengo & Kathryn E. Kemper & Michael E. Goddard & Naomi R. Wray & Peter M. Visscher & Jian Yang, 2021. "Widespread signatures of natural selection across human complex traits and functional genomic categories," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    12. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    13. Heli Julkunen & Anna Cichońska & Mika Tiainen & Harri Koskela & Kristian Nybo & Valtteri Mäkelä & Jussi Nokso-Koivisto & Kati Kristiansson & Markus Perola & Veikko Salomaa & Pekka Jousilahti & Annamar, 2023. "Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Hamilton Se-Hwee Oh & Jarod Rutledge & Daniel Nachun & Róbert Pálovics & Olamide Abiose & Patricia Moran-Losada & Divya Channappa & Deniz Yagmur Urey & Kate Kim & Yun Ju Sung & Lihua Wang & Jigyasha T, 2023. "Organ aging signatures in the plasma proteome track health and disease," Nature, Nature, vol. 624(7990), pages 164-172, December.
    15. Mitja I. Kurki & Juha Karjalainen & Priit Palta & Timo P. Sipilä & Kati Kristiansson & Kati M. Donner & Mary P. Reeve & Hannele Laivuori & Mervi Aavikko & Mari A. Kaunisto & Anu Loukola & Elisa Lahtel, 2023. "FinnGen provides genetic insights from a well-phenotyped isolated population," Nature, Nature, vol. 613(7944), pages 508-518, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Shiyu Zhang & Zheng Wang & Yijing Wang & Yixiao Zhu & Qiao Zhou & Xingxing Jian & Guihu Zhao & Jian Qiu & Kun Xia & Beisha Tang & Julian Mutz & Jinchen Li & Bin Li, 2024. "A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Yuji Yamamoto & Yuya Shirai & Kyuto Sonehara & Shinichi Namba & Takafumi Ojima & Kenichi Yamamoto & Ryuya Edahiro & Ken Suzuki & Akinori Kanai & Yoshiya Oda & Yutaka Suzuki & Takayuki Morisaki & Akira, 2025. "Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    3. Peng Ren & Xiao-He Hou & Zeyu Li & Jia You & Yuzhu Li & Wei Zhang & Weikang Gong & Bei Zhang & Bangsheng Wu & Linbo Wang & Chun Shen & Yujie Zhao & Qing Ma & Jujiao Kang & Yuchao Jiang & Neil Roberts , 2025. "Atlas of proteomic signatures of brain structure and its links to brain disorders," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    4. Alexander T. Williams & Jing Chen & Kayesha Coley & Chiara Batini & Abril Izquierdo & Richard Packer & Erik Abner & Stavroula Kanoni & David J. Shepherd & Robert C. Free & Edward J. Hollox & Nigel J. , 2023. "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Bingxin Zhao & Yujue Li & Zirui Fan & Zhenyi Wu & Juan Shu & Xiaochen Yang & Yilin Yang & Xifeng Wang & Bingxuan Li & Xiyao Wang & Carlos Copana & Yue Yang & Jinjie Lin & Yun Li & Jason L. Stein & Joa, 2024. "Eye-brain connections revealed by multimodal retinal and brain imaging genetics," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    6. Yon Ho Jee & Ying Wang & Keum Ji Jung & Ji-Young Lee & Heejin Kimm & Rui Duan & Alkes L. Price & Alicia R. Martin & Peter Kraft, 2025. "Genome-wide association studies in a large Korean cohort identify quantitative trait loci for 36 traits and illuminate their genetic architectures," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    7. Douglas P. Loesch & Manik Garg & Dorota Matelska & Dimitrios Vitsios & Xiao Jiang & Scott C. Ritchie & Benjamin B. Sun & Heiko Runz & Christopher D. Whelan & Rury R. Holman & Robert J. Mentz & Filipe , 2025. "Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    8. Xi Cao & Minghui Jiang & Yunlong Guan & Si Li & Chen Duan & Yan Gong & Yifan Kong & Zhonghe Shao & Hongji Wu & Xiangyang Yao & Bo Li & Miao Wang & Hua Xu & Xingjie Hao, 2025. "Trans-ancestry GWAS identifies 59 loci and improves risk prediction and fine-mapping for kidney stone disease," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    9. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Yash Patel & Jean Shin & Eeva Sliz & Ariana Tang & Aniket Mishra & Rui Xia & Edith Hofer & Hema Sekhar Reddy Rajula & Ruiqi Wang & Frauke Beyer & Katrin Horn & Max Riedl & Jing Yu & Henry Völzke & Rob, 2024. "Genetic risk factors underlying white matter hyperintensities and cortical atrophy," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    11. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Ruoyu Tian & Tian Ge & Hyeokmoon Kweon & Daniel B. Rocha & Max Lam & Jimmy Z. Liu & Kritika Singh & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Ellen A. Tsai & Hailiang Huang & Christopher F., 2024. "Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Abolfazl Doostparast Torshizi & Dongnhu T. Truong & Liping Hou & Bart Smets & Christopher D. Whelan & Shuwei Li, 2024. "Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson’s disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Andras Gezsi & Sandra Auwera & Hannu Mäkinen & Nora Eszlari & Gabor Hullam & Tamas Nagy & Sarah Bonk & Rubèn González-Colom & Xenia Gonda & Linda Garvert & Teemu Paajanen & Zsofia Gal & Kevin Kirchner, 2024. "Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Xiao-Yu He & Bang-Sheng Wu & Liu Yang & Yu Guo & Yue-Ting Deng & Ze-Yu Li & Chen-Jie Fei & Wei-Shi Liu & Yi-Jun Ge & Jujiao Kang & Jianfeng Feng & Wei Cheng & Qiang Dong & Jin-Tai Yu, 2024. "Genetic associations of protein-coding variants in venous thromboembolism," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    16. Caitlin E. Carey & Rebecca Shafee & Robbee Wedow & Amanda Elliott & Duncan S. Palmer & John Compitello & Masahiro Kanai & Liam Abbott & Patrick Schultz & Konrad J. Karczewski & Samuel C. Bryant & Caro, 2024. "Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation," Nature Human Behaviour, Nature, vol. 8(8), pages 1599-1615, August.
    17. Wenbo Jiang & Hang Wang & Yiding Geng & Meijuan Guo & Yingdong Zuo & Sijia Han & Zijie Liu & Shuaijun Chen & Shuzhen Fan & Shangying Li & Conghui Qiao & Qianzhu Li & Bai Li & Yunpeng Zhang & Wei Wei &, 2025. "The health impacts and genetic architecture of food liking in cardio-metabolic diseases," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    18. Dennis Meer & Zillur Rahman & Aigar Ottas & Pravesh Parekh & Gleda Kutrolli & Sara E. Stinson & Maria Koromina & Jaroslav Rokicki & Ida E. Sønderby & Nadine Parker & Markos Tesfaye & Guy Hindley & Lin, 2025. "Pleiotropic and sex-specific genetic mechanisms of circulating metabolic markers," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    19. Anand E. Rajesh & Abraham Olvera-Barrios & Alasdair N. Warwick & Yue Wu & Kelsey V. Stuart & Mahantesh I. Biradar & Chuin Ying Ung & Anthony P. Khawaja & Robert Luben & Paul J. Foster & Charles R. Cle, 2025. "Machine learning derived retinal pigment score from ophthalmic imaging shows ethnicity is not biology," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    20. V. E. Jackson & Y. Wu & R. Bonelli & J. P. Owen & L. W. Scott & S. Farashi & Y. Kihara & M. L. Gantner & C. Egan & K. M. Williams & B. R. E. Ansell & A. Tufail & A. Y. Lee & M. Bahlo, 2025. "Multi-omic spatial effects on high-resolution AI-derived retinal thickness," Nature Communications, Nature, vol. 16(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59964-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.