IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45421-w.html
   My bibliography  Save this article

Detection of senescence using machine learning algorithms based on nuclear features

Author

Listed:
  • Imanol Duran

    (Du Cane Road
    Du Cane Road)

  • Joaquim Pombo

    (Du Cane Road
    Du Cane Road)

  • Bin Sun

    (Du Cane Road
    Du Cane Road)

  • Suchira Gallage

    (Du Cane Road
    Du Cane Road
    German Cancer Research Center (DKFZ), Heidelberg
    University of Tuebingen)

  • Hiromi Kudo

    (Imperial College London)

  • Domhnall McHugh

    (Du Cane Road
    Du Cane Road)

  • Laura Bousset

    (Du Cane Road
    Du Cane Road)

  • Jose Efren Barragan Avila

    (German Cancer Research Center (DKFZ), Heidelberg)

  • Roberta Forlano

    (Imperial College London)

  • Pinelopi Manousou

    (Imperial College London)

  • Mathias Heikenwalder

    (German Cancer Research Center (DKFZ), Heidelberg
    University of Tuebingen
    Eberhard Karls University)

  • Dominic J. Withers

    (Du Cane Road
    Du Cane Road)

  • Santiago Vernia

    (Du Cane Road
    Du Cane Road)

  • Robert D. Goldin

    (Imperial College London)

  • Jesús Gil

    (Du Cane Road
    Du Cane Road)

Abstract

Cellular senescence is a stress response with broad pathophysiological implications. Senotherapies can induce senescence to treat cancer or eliminate senescent cells to ameliorate ageing and age-related pathologies. However, the success of senotherapies is limited by the lack of reliable ways to identify senescence. Here, we use nuclear morphology features of senescent cells to devise machine-learning classifiers that accurately predict senescence induced by diverse stressors in different cell types and tissues. As a proof-of-principle, we use these senescence classifiers to characterise senolytics and to screen for drugs that selectively induce senescence in cancer cells but not normal cells. Moreover, a tissue senescence score served to assess the efficacy of senolytic drugs and identified senescence in mouse models of liver cancer initiation, ageing, and fibrosis, and in patients with fatty liver disease. Thus, senescence classifiers can help to detect pathophysiological senescence and to discover and validate potential senotherapies.

Suggested Citation

  • Imanol Duran & Joaquim Pombo & Bin Sun & Suchira Gallage & Hiromi Kudo & Domhnall McHugh & Laura Bousset & Jose Efren Barragan Avila & Roberta Forlano & Pinelopi Manousou & Mathias Heikenwalder & Domi, 2024. "Detection of senescence using machine learning algorithms based on nuclear features," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45421-w
    DOI: 10.1038/s41467-024-45421-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45421-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-45421-w?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. Tae-Won Kang & Tetyana Yevsa & Norman Woller & Lisa Hoenicke & Torsten Wuestefeld & Daniel Dauch & Anja Hohmeyer & Marcus Gereke & Ramona Rudalska & Anna Potapova & Marcus Iken & Mihael Vucur & Siegfr, 2011. "Senescence surveillance of pre-malignant hepatocytes limits liver cancer development," Nature, Nature, vol. 479(7374), pages 547-551, November.
    2. Mikolaj Ogrodnik & Satomi Miwa & Tamar Tchkonia & Dina Tiniakos & Caroline L. Wilson & Albert Lahat & Christoper P. Day & Alastair Burt & Allyson Palmer & Quentin M. Anstee & Sushma Nagaraja Grellsche, 2017. "Cellular senescence drives age-dependent hepatic steatosis," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    3. Reut Yosef & Noam Pilpel & Ronit Tokarsky-Amiel & Anat Biran & Yossi Ovadya & Snir Cohen & Ezra Vadai & Liat Dassa & Elisheva Shahar & Reba Condiotti & Ittai Ben-Porath & Valery Krizhanovsky, 2016. "Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    4. Dai Kusumoto & Tomohisa Seki & Hiromune Sawada & Akira Kunitomi & Toshiomi Katsuki & Mai Kimura & Shogo Ito & Jin Komuro & Hisayuki Hashimoto & Keiichi Fukuda & Shinsuke Yuasa, 2021. "Anti-senescent drug screening by deep learning-based morphology senescence scoring," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Cun Wang & Serena Vegna & Haojie Jin & Bente Benedict & Cor Lieftink & Christel Ramirez & Rodrigo Leite Oliveira & Ben Morris & Jules Gadiot & Wei Wang & Aimée Chatinier & Liqin Wang & Dongmei Gao & B, 2019. "Inducing and exploiting vulnerabilities for the treatment of liver cancer," Nature, Nature, vol. 574(7777), pages 268-272, October.
    6. Corina Amor & Judith Feucht & Josef Leibold & Yu-Jui Ho & Changyu Zhu & Direna Alonso-Curbelo & Jorge Mansilla-Soto & Jacob A. Boyer & Xiang Li & Theodoros Giavridis & Amanda Kulick & Shauna Houlihan , 2020. "Senolytic CAR T cells reverse senescence-associated pathologies," Nature, Nature, vol. 583(7814), pages 127-132, July.
    7. Darren J. Baker & Bennett G. Childs & Matej Durik & Melinde E. Wijers & Cynthia J. Sieben & Jian Zhong & Rachel A. Saltness & Karthik B. Jeganathan & Grace Casaclang Verzosa & Abdulmohammad Pezeshki &, 2016. "Naturally occurring p16Ink4a-positive cells shorten healthy lifespan," Nature, Nature, vol. 530(7589), pages 184-189, February.
    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. Ines Sturmlechner & Chance C. Sine & Karthik B. Jeganathan & Cheng Zhang & Raul O. Fierro Velasco & Darren J. Baker & Hu Li & Jan M. Deursen, 2022. "Senescent cells limit p53 activity via multiple mechanisms to remain viable," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Toshiyuki Ko & Seitaro Nomura & Shintaro Yamada & Kanna Fujita & Takanori Fujita & Masahiro Satoh & Chio Oka & Manami Katoh & Masamichi Ito & Mikako Katagiri & Tatsuro Sassa & Bo Zhang & Satoshi Hatsu, 2022. "Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Ross J. Hill & Nazareno Bona & Job Smink & Hannah K. Webb & Alastair Crisp & Juan I. Garaycoechea & Gerry P. Crossan, 2024. "p53 regulates diverse tissue-specific outcomes to endogenous DNA damage in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Vanessa Smer-Barreto & Andrea Quintanilla & Richard J. R. Elliott & John C. Dawson & Jiugeng Sun & Víctor M. Campa & Álvaro Lorente-Macías & Asier Unciti-Broceta & Neil O. Carragher & Juan Carlos Acos, 2023. "Discovery of senolytics using machine learning," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Madison L. Doolittle & Dominik Saul & Japneet Kaur & Jennifer L. Rowsey & Stephanie J. Vos & Kevin D. Pavelko & Joshua N. Farr & David G. Monroe & Sundeep Khosla, 2023. "Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Christel F. A. Ramirez & Daniel Taranto & Masami Ando-Kuri & Marnix H. P. Groot & Efi Tsouri & Zhijie Huang & Daniel Groot & Roelof J. C. Kluin & Daan J. Kloosterman & Joanne Verheij & Jing Xu & Seren, 2024. "Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    7. Carlos Anerillas & Allison B. Herman & Rachel Munk & Amanda Garrido & Kwan-Wood Gabriel Lam & Matthew J. Payea & Martina Rossi & Dimitrios Tsitsipatis & Jennifer L. Martindale & Yulan Piao & Krystyna , 2022. "A BDNF-TrkB autocrine loop enhances senescent cell viability," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Rana Salam & Alexa Saliou & Franck Bielle & Mathilde Bertrand & Christophe Antoniewski & Catherine Carpentier & Agusti Alentorn & Laurent Capelle & Marc Sanson & Emmanuelle Huillard & Léa Bellenger & , 2023. "Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    9. Cox, Lynne S., 2022. "Therapeutic approaches to treat and prevent age-related diseases through understanding the underlying biological drivers of ageing," The Journal of the Economics of Ageing, Elsevier, vol. 23(C).
    10. Vanessa Rousseau & Elias Einig & Chao Jin & Julia Horn & Mathias Riebold & Tanja Poth & Mohamed-Ali Jarboui & Michael Flentje & Nikita Popov, 2023. "Trim33 masks a non-transcriptional function of E2f4 in replication fork progression," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Jaskaren Kohli & Chen Ge & Eleni Fitsiou & Miriam Doepner & Simone M. Brandenburg & William J. Faller & Todd W. Ridky & Marco Demaria, 2022. "Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Gorshkov, Vyacheslav & Privman, Vladimir & Libert, Sergiy, 2016. "Lattice percolation approach to 3D modeling of tissue aging," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 462(C), pages 207-216.
    13. Eliska Vacurova & Jaroslava Trnovska & Petr Svoboda & Vojtech Skop & Vendula Novosadova & David Pajuelo Reguera & Silvia Petrezselyová & Benoit Piavaux & Berwini Endaya & Frantisek Spoutil & Dagmar Zu, 2022. "Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    14. Leighton H. Daigh & Debarya Saha & David L. Rosenthal & Katherine R. Ferrick & Tobias Meyer, 2024. "Uncoupling of mTORC1 from E2F activity maintains DNA damage and senescence," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    15. Shujuan Yu & Yaqun Sui & Jiawei Wang & Yongdong Li & Hanlin Li & Yingping Cao & Liqing Chen & Longguang Jiang & Cai Yuan & Mingdong Huang, 2022. "Crystal structure and cellular functions of uPAR dimer," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    16. Yukinari Haraoka & Yuki Akieda & Yuri Nagai & Chihiro Mogi & Tohru Ishitani, 2022. "Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Nanase Igarashi & Kenichi Miyata & Tze Mun Loo & Masatomo Chiba & Aki Hanyu & Mika Nishio & Hiroko Kawasaki & Hao Zheng & Shinya Toyokuni & Shunsuke Kon & Keiji Moriyama & Yasuyuki Fujita & Akiko Taka, 2022. "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    18. Yudong Fu & Fan Jiang & Xiao Zhang & Yingyi Pan & Rui Xu & Xiu Liang & Xiaofen Wu & Xingqiang Li & Kaixuan Lin & Ruona Shi & Xiaofei Zhang & Dominique Ferrandon & Jing Liu & Duanqing Pei & Jie Wang & , 2024. "Perturbation of METTL1-mediated tRNA N7- methylguanosine modification induces senescence and aging," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    19. Xu Zhang & Vesselina M. Pearsall & Chase M. Carver & Elizabeth J. Atkinson & Benjamin D. S. Clarkson & Ethan M. Grund & Michelle Baez-Faria & Kevin D. Pavelko & Jennifer M. Kachergus & Thomas A. White, 2022. "Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    20. Benjamin Assouline & Rachel Kahn & Lutfi Hodali & Reba Condiotti & Yarden Engel & Ela Elyada & Tzlil Mordechai-Heyn & Jason R. Pitarresi & Dikla Atias & Eliana Steinberg & Tirza Bidany-Mizrahi & Esthe, 2024. "Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8+ T cell activation and limit responsiveness to immunotherapy in mice," 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_s41467-024-45421-w. 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.