IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47316-2.html
   My bibliography  Save this article

Nonlinear DNA methylation trajectories in aging male mice

Author

Listed:
  • Maja Olecka

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Alena Bömmel

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Lena Best

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Madlen Haase

    (Jena University Hospital)

  • Silke Foerste

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Konstantin Riege

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Thomas Dost

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Stefano Flor

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Otto W. Witte

    (Jena University Hospital)

  • Sören Franzenburg

    (Kiel University and University Medical Center Schleswig-Holstein)

  • Marco Groth

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Björn Eyss

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

  • Christoph Kaleta

    (University of Kiel and University Medical Center Schleswig-Holstein)

  • Christiane Frahm

    (Jena University Hospital)

  • Steve Hoffmann

    (Leibniz Institute on Aging - Fritz Lipmann Institute (FLI))

Abstract

Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigate the methylation trajectories of male mouse colon at five different time points of aging. Our study indicates the existence of sudden hypermethylation events at specific stages of life. Precisely, we identify two epigenomic switches during early-to-midlife (3-9 months) and mid-to-late-life (15-24 months) transitions, separating the rodents’ life into three stages. These nonlinear methylation dynamics predominantly affect genes associated with the nervous system and enrich in bivalently marked chromatin regions. Based on groups of nonlinearly modified loci, we construct a clock-like classifier STageR (STage of aging estimatoR) that accurately predicts murine epigenetic stage. We demonstrate the universality of our clock in an independent mouse cohort and with publicly available datasets.

Suggested Citation

  • Maja Olecka & Alena Bömmel & Lena Best & Madlen Haase & Silke Foerste & Konstantin Riege & Thomas Dost & Stefano Flor & Otto W. Witte & Sören Franzenburg & Marco Groth & Björn Eyss & Christoph Kaleta , 2024. "Nonlinear DNA methylation trajectories in aging male mice," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47316-2
    DOI: 10.1038/s41467-024-47316-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47316-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-47316-2?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. Michael Lawrence & Wolfgang Huber & Hervé Pagès & Patrick Aboyoun & Marc Carlson & Robert Gentleman & Martin T Morgan & Vincent J Carey, 2013. "Software for Computing and Annotating Genomic Ranges," PLOS Computational Biology, Public Library of Science, vol. 9(8), pages 1-10, August.
    2. David R. Bentley & Shankar Balasubramanian & Harold P. Swerdlow & Geoffrey P. Smith & John Milton & Clive G. Brown & Kevin P. Hall & Dirk J. Evers & Colin L. Barnes & Helen R. Bignell & Jonathan M. Bo, 2008. "Accurate whole human genome sequencing using reversible terminator chemistry," Nature, Nature, vol. 456(7218), pages 53-59, November.
    3. Thomas Montavon & Nicholas Shukeir & Galina Erikson & Bettina Engist & Megumi Onishi-Seebacher & Devon Ryan & Yaarub Musa & Gerhard Mittler & Alexandra Graff Meyer & Christel Genoud & Thomas Jenuwein, 2021. "Complete loss of H3K9 methylation dissolves mouse heterochromatin organization," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    4. Laetitia Mazelin & Agnès Bernet & Christelle Bonod-Bidaud & Laurent Pays & Ségolène Arnaud & Christian Gespach & Dale E Bredesen & Jean-Yves Scoazec & Patrick Mehlen, 2004. "Netrin-1 controls colorectal tumorigenesis by regulating apoptosis," Nature, Nature, vol. 431(7004), pages 80-84, September.
    5. Peer Aramillo Irizar & Sascha Schäuble & Daniela Esser & Marco Groth & Christiane Frahm & Steffen Priebe & Mario Baumgart & Nils Hartmann & Shiva Marthandan & Uwe Menzel & Jule Müller & Silvio Schmidt, 2018. "Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    6. Hervé Tricoire & Michael Rera, 2015. "A New, Discontinuous 2 Phases of Aging Model: Lessons from Drosophila melanogaster," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-14, November.
    7. Xuran Wang & Jihwan Park & Katalin Susztak & Nancy R. Zhang & Mingyao Li, 2019. "Bulk tissue cell type deconvolution with multi-subject single-cell expression reference," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    8. Huan Lian & Jin Wei & Ru Zang & Wen Ye & Qing Yang & Xia-Nan Zhang & Yun-Da Chen & Yu-Zhi Fu & Ming-Ming Hu & Cao-Qi Lei & Wei-Wei Luo & Shu Li & Hong-Bing Shu, 2018. "ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    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. Raúl F. Pérez & Patricia Tezanos & Alfonso Peñarroya & Alejandro González-Ramón & Rocío G. Urdinguio & Javier Gancedo-Verdejo & Juan Ramón Tejedor & Pablo Santamarina-Ojeda & Juan José Alba-Linares & , 2024. "A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    2. Kobe Ridder & Huiwen Che & Kaat Leroy & Bernard Thienpont, 2024. "Benchmarking of methods for DNA methylome deconvolution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Fiaz Ahmad Sulehri & Saba Sharif, 2022. "The Impact of Firm Sustainability on Firm Growth: Evidence from USA," Journal of Policy Research (JPR), Research Foundation for Humanity (RFH), vol. 8(2), pages 1-15, August.
    4. Jakob Hartmann & Thomas Bajaj & Joy Otten & Claudia Klengel & Tim Ebert & Anne-Kathrin Gellner & Ellen Junglas & Kathrin Hafner & Elmira A. Anderzhanova & Fiona Tang & Galen Missig & Lindsay Rexrode &, 2024. "SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Bárbara Andrade Barbosa & Saskia D. Asten & Ji Won Oh & Arantza Farina-Sarasqueta & Joanne Verheij & Frederike Dijk & Hanneke W. M. Laarhoven & Bauke Ylstra & Juan J. Garcia Vallejo & Mark A. Wiel & Y, 2021. "Bayesian log-normal deconvolution for enhanced in silico microdissection of bulk gene expression data," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    6. Poonam Dhillon & Kelly Ann Mulholland & Hailong Hu & Jihwan Park & Xin Sheng & Amin Abedini & Hongbo Liu & Allison Vassalotti & Junnan Wu & Katalin Susztak, 2023. "Increased levels of endogenous retroviruses trigger fibroinflammation and play a role in kidney disease development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. Gaylor Boulay & Liliane C. Broye & Rui Dong & Sowmya Iyer & Rajendran Sanalkumar & Yu-Hang Xing & Rémi Buisson & Shruthi Rengarajan & Beverly Naigles & Benoît Duc & Angela Volorio & Mary E. Awad & Raf, 2024. "EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    11. Nelson Johansen & Hongru Hu & Gerald Quon, 2023. "Projecting RNA measurements onto single cell atlases to extract cell type-specific expression profiles using scProjection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Xiaohe Lin & Junjie Yin & Yifan Wang & Jing Yao & Qingshun Q. Li & Vit Latzel & Oliver Bossdorf & Yuan-Ye Zhang, 2024. "Environment-induced heritable variations are common in Arabidopsis thaliana," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Jingtao Wang & Gregory J. Fonseca & Jun Ding, 2024. "scSemiProfiler: Advancing large-scale single-cell studies through semi-profiling with deep generative models and active learning," Nature Communications, Nature, vol. 15(1), pages 1-27, December.
    14. Quentin I. B. Lemaître & Natascha Bartsch & Ian U. Kouzel & Henriette Busengdal & Gemma Sian Richards & Patrick R. H. Steinmetz & Fabian Rentzsch, 2023. "NvPrdm14d-expressing neural progenitor cells contribute to non-ectodermal neurogenesis in Nematostella vectensis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Songming Tang & Xuejian Cui & Rongxiang Wang & Sijie Li & Siyu Li & Xin Huang & Shengquan Chen, 2024. "scCASE: accurate and interpretable enhancement for single-cell chromatin accessibility sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Yanming Ren & Zongyao Huang & Lingling Zhou & Peng Xiao & Junwei Song & Ping He & Chuanxing Xie & Ran Zhou & Menghan Li & Xiangqun Dong & Qing Mao & Chao You & Jianguo Xu & Yanhui Liu & Zhigang Lan & , 2023. "Spatial transcriptomics reveals niche-specific enrichment and vulnerabilities of radial glial stem-like cells in malignant gliomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    17. Tiago C. Luis & Nikolaos Barkas & Joana Carrelha & Alice Giustacchini & Stefania Mazzi & Ruggiero Norfo & Bishan Wu & Affaf Aliouat & Jose A. Guerrero & Alba Rodriguez-Meira & Tiphaine Bouriez-Jones &, 2023. "Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    18. Chang Su & Zichun Xu & Xinning Shan & Biao Cai & Hongyu Zhao & Jingfei Zhang, 2023. "Cell-type-specific co-expression inference from single cell RNA-sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    19. Michael R. Kelly & Kamila Wisniewska & Matthew J. Regner & Michael W. Lewis & Andrea A. Perreault & Eric S. Davis & Douglas H. Phanstiel & Joel S. Parker & Hector L. Franco, 2022. "A multi-omic dissection of super-enhancer driven oncogenic gene expression programs in ovarian cancer," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    20. Seoyeon Lee & Mohammad Naimul Islam & Kaveh Boostanpour & Dvir Aran & Guangchun Jin & Stephanie Christenson & Michael A. Matthay & Walter L. Eckalbar & Daryle J. DePianto & Joseph R. Arron & Liam Mage, 2021. "Molecular programs of fibrotic change in aging human lung," Nature Communications, Nature, vol. 12(1), pages 1-10, 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:15:y:2024:i:1:d:10.1038_s41467-024-47316-2. 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.