IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49007-4.html
   My bibliography  Save this article

Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease

Author

Listed:
  • Santiago E. Sanchez

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University
    Stanford University School of Medicine)

  • Yuchao Gu

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Yan Wang

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

  • Anudeep Golla

    (Stanford University School of Medicine)

  • Annika Martin

    (University of California)

  • William Shomali

    (Stanford University School of Medicine)

  • Dirk Hockemeyer

    (University of California
    Chan Zuckerberg Biohub
    University of California, Berkeley)

  • Sharon A. Savage

    (National Cancer Institute)

  • Steven E. Artandi

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement (DTM) by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and de novo elongation with up to 30 bp resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance. We find that human aging is accompanied by a progressive loss of long telomeres and an accumulation of shorter telomeres. In patients with defects in telomere maintenance, the accumulation of short telomeres is more pronounced and correlates with phenotypic severity. We apply machine learning to train a binary classification model that distinguishes healthy individuals from those with telomere biology disorders. This sequencing and bioinformatic pipeline will advance our understanding of telomere maintenance mechanisms and the use of telomere length as a clinical biomarker of aging and disease.

Suggested Citation

  • Santiago E. Sanchez & Yuchao Gu & Yan Wang & Anudeep Golla & Annika Martin & William Shomali & Dirk Hockemeyer & Sharon A. Savage & Steven E. Artandi, 2024. "Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49007-4
    DOI: 10.1038/s41467-024-49007-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49007-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-49007-4?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. Tsung-Po Lai & Ning Zhang & Jungsik Noh & Ilgen Mender & Enzo Tedone & Ejun Huang & Woodring E. Wright & Gaudenz Danuser & Jerry W. Shay, 2017. "A method for measuring the distribution of the shortest telomeres in cells and tissues," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    2. Steven E. Artandi & Sandy Chang & Shwu-Luan Lee & Scott Alson & Geoffrey J. Gottlieb & Lynda Chin & Ronald A. DePinho, 2000. "Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice," Nature, Nature, vol. 406(6796), pages 641-645, August.
    3. Tom Vulliamy & Anna Marrone & Frederick Goldman & Andrew Dearlove & Monica Bessler & Philip J. Mason & Inderjeet Dokal, 2001. "The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita," Nature, Nature, vol. 413(6854), pages 432-435, September.
    4. Joe Nassour & Robert Radford & Adriana Correia & Javier Miralles Fusté & Brigitte Schoell & Anna Jauch & Reuben J. Shaw & Jan Karlseder, 2019. "Autophagic cell death restricts chromosomal instability during replicative crisis," Nature, Nature, vol. 565(7741), pages 659-663, 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. Timothy K. Turkalo & Antonio Maffia & Johannes J. Schabort & Samuel G. Regalado & Mital Bhakta & Marco Blanchette & Diana C. J. Spierings & Peter M. Lansdorp & Dirk Hockemeyer, 2023. "A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Tobias T. Schmidt & Carly Tyer & Preeyesh Rughani & Candy Haggblom & Jeffrey R. Jones & Xiaoguang Dai & Kelly A. Frazer & Fred H. Gage & Sissel Juul & Scott Hickey & Jan Karlseder, 2024. "High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Ilaria Rosso & Corey Jones-Weinert & Francesca Rossiello & Matteo Cabrini & Silvia Brambillasca & Leonel Munoz-Sagredo & Zeno Lavagnino & Emanuele Martini & Enzo Tedone & Massimiliano Garre’ & Julio A, 2023. "Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Riham Smoom & Catherine Lee May & Vivian Ortiz & Mark Tigue & Hannah M. Kolev & Melissa Rowe & Yitzhak Reizel & Ashleigh Morgan & Nachshon Egyes & Dan Lichtental & Emmanuel Skordalakes & Klaus H. Kaes, 2023. "Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    6. Alyssa R Lindrose & Lauren W Y McLester-Davis & Renee I Tristano & Leila Kataria & Shahinaz M Gadalla & Dan T A Eisenberg & Simon Verhulst & Stacy Drury, 2021. "Method comparison studies of telomere length measurement using qPCR approaches: A critical appraisal of the literature," PLOS ONE, Public Library of Science, vol. 16(1), pages 1-23, January.
    7. Rishi Kumar Nageshan & Raquel Ortega & Nevan Krogan & Julia Promisel Cooper, 2024. "Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Natthakan Thongon & Feiyang Ma & Andrea Santoni & Matteo Marchesini & Elena Fiorini & Ashley Rose & Vera Adema & Irene Ganan-Gomez & Emma M. Groarke & Fernanda Gutierrez-Rodrigues & Shuaitong Chen & P, 2021. "Hematopoiesis under telomere attrition at the single-cell resolution," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    9. Angela M. Hinchie & Samantha L. Sanford & Kelly E. Loughridge & Rachel M. Sutton & Anishka H. Parikh & Agustin A. Gil Silva & Daniel I. Sullivan & Pattra Chun-On & Matthew R. Morrell & John F. McDyer , 2024. "A persistent variant telomere sequence in a human pedigree," Nature Communications, Nature, vol. 15(1), pages 1-16, 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_s41467-024-49007-4. 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.