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The central role of DNA damage in the ageing process

Author

Listed:
  • Björn Schumacher

    (University of Cologne
    University of Cologne)

  • Joris Pothof

    (Erasmus University Medical Center)

  • Jan Vijg

    (Albert Einstein College of Medicine, Bronx
    Shanghai Jiao Tong University School of Medicine)

  • Jan H. J. Hoeijmakers

    (University of Cologne
    University of Cologne
    Erasmus University Medical Center
    Oncode Institute)

Abstract

Ageing is a complex, multifaceted process leading to widespread functional decline that affects every organ and tissue, but it remains unknown whether ageing has a unifying causal mechanism or is grounded in multiple sources. Phenotypically, the ageing process is associated with a wide variety of features at the molecular, cellular and physiological level—for example, genomic and epigenomic alterations, loss of proteostasis, declining overall cellular and subcellular function and deregulation of signalling systems. However, the relative importance, mechanistic interrelationships and hierarchical order of these features of ageing have not been clarified. Here we synthesize accumulating evidence that DNA damage affects most, if not all, aspects of the ageing phenotype, making it a potentially unifying cause of ageing. Targeting DNA damage and its mechanistic links with the ageing phenotype will provide a logical rationale for developing unified interventions to counteract age-related dysfunction and disease.

Suggested Citation

  • Björn Schumacher & Joris Pothof & Jan Vijg & Jan H. J. Hoeijmakers, 2021. "The central role of DNA damage in the ageing process," Nature, Nature, vol. 592(7856), pages 695-703, April.
    • Handle: RePEc:nat:nature:v:592:y:2021:i:7856:d:10.1038_s41586-021-03307-7
    DOI: 10.1038/s41586-021-03307-7
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    Cited by:

    1. Yu-Wei Luo & Jiang-Peng Zhou & Hongyu Ji & Doudou Xu & Anqi Zheng & Xin Wang & Zhizheng Dai & Zhicheng Luo & Fang Cao & Xing-Yue Wang & Yunfang Bai & Di Chen & Yueming Chen & Qi Wang & Yaying Yang & X, 2024. "SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Huiru Bai & Xiaoqin Liu & Meizhen Lin & Yuan Meng & Ruolan Tang & Yajing Guo & Nan Li & Michael F. Clarke & Shang Cai, 2024. "Progressive senescence programs induce intrinsic vulnerability to aging-related female breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Diana A. Llerena Schiffmacher & Shun-Hsiao Lee & Katarzyna W. Kliza & Arjan F. Theil & Masaki Akita & Angela Helfricht & Karel Bezstarosti & Camila Gonzalo-Hansen & Haico Attikum & Matty Verlaan-de Vr, 2024. "The small CRL4CSA ubiquitin ligase component DDA1 regulates transcription-coupled repair dynamics," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
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    5. Pradeep Ramalingam & Michael C. Gutkin & Michael G. Poulos & Taylor Tillery & Chelsea Doughty & Agatha Winiarski & Ana G. Freire & Shahin Rafii & David Redmond & Jason M. Butler, 2023. "Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Galván, Antonio & Haas, Jannik & Moreno-Leiva, Simón & Osorio-Aravena, Juan Carlos & Nowak, Wolfgang & Palma-Benke, Rodrigo & Breyer, Christian, 2022. "Exporting sunshine: Planning South America’s electricity transition with green hydrogen," Applied Energy, Elsevier, vol. 325(C).
    7. Mahdi Moqri & Andrea Cipriano & Daniel J. Simpson & Sajede Rasouli & Tara Murty & Tineke Anna Jong & Daniel Nachun & Guilherme Sena Brandine & Kejun Ying & Andrei Tarkhov & Karolina A. Aberg & Edwin O, 2024. "PRC2-AgeIndex as a universal biomarker of aging and rejuvenation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Tianyu Zhu & Huige Tong & Zhaozhen Du & Stephan Beck & Andrew E. Teschendorff, 2024. "An improved epigenetic counter to track mitotic age in normal and precancerous tissues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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