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Studying Werner syndrome to elucidate mechanisms and therapeutics of human aging and age-related diseases

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Abstract

Aging is a natural and unavoidable part of life. However, aging is also the primary driver of the dominant human diseases, such as cardiovascular disease, cancer, and neurodegenerative diseases, including Alzheimer’s disease. Unraveling the sophisticated molecular mechanisms of the human aging process may provide novel strategies to extend ‘healthy aging’ and the cure of human aging-related diseases. Werner syndrome (WS), is a heritable human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. As a classical premature aging disease, etiological exploration of WS can shed light on the mechanisms of normal human aging and facilitate the development of interventional strategies to improve healthspan. Here, we summarize the latest progress of the molecular understandings of WRN protein, highlight the advantages of using different WS model systems, including Caenorhabditis elegans, Drosophila melanogaster and induced pluripotent stem cell (iPSC) systems. Further studies on WS will propel drug development for WS patients, and possibly also for normal age-related diseases.

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Acknowledgements

We acknowledge the work of the many researchers whose published papers we were unable to cite due to space limitations. We thank Prof. Vilhelm Bohr at the National Institute on Aging for critical reading of the manuscript. This research was supported by the HELSE SøR-ØST, Norway (E.F.F., #2017056), The Research Council of Norway (E.F.F., #262175 and #277813), and The Hong Kong General Research Fund (H.H.C. and W.Y.C., #Project Number 14121618) of the Research Grants Council. The E.F.F. Laboratory has CRADA arrangements with ChromaDex.

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  1. Sofie Lautrup and Domenica Caponio are Co-first authors.

Authors and Affiliations

  1. Department of Clinical Molecular Biology, Faculty of Medicine, University of Oslo, Oslo, Norway

    Sofie Lautrup, Domenica Caponio & Evandro F. Fang

  2. EpiGen, Akershus University Hospital, 1478, Lørenskog, Norway

    Sofie Lautrup, Domenica Caponio & Evandro F. Fang

  3. Department of Clinical and Experimental Medicine, University of Foggia Medical School, Via L.Pinto, 171122, Foggia, Italy

    Domenica Caponio & Claudia Piccoli

  4. CUHK-CAS GIBH Joint Research Laboratory on Stem Cell and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong S.A.R., China

    Hoi-Hung Cheung & Wai-Yee Chan

  5. Laboratory of Pre-clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028, Rionero in Vulture, Italy

    Claudia Piccoli

  6. Department of Molecular Biology and Genetics, Danish Aging Research Center, University of Aarhus, 8000, Aarhus C, Denmark

    Tinna Stevnsner

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Lautrup, S., Caponio, D., Cheung, HH. et al. Studying Werner syndrome to elucidate mechanisms and therapeutics of human aging and age-related diseases. Biogerontology 20, 255–269 (2019). https://doi.org/10.1007/s10522-019-09798-2

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