4.4 Review

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

Journal

BIOGERONTOLOGY
Volume 20, Issue 3, Pages 255-269

Publisher

SPRINGER
DOI: 10.1007/s10522-019-09798-2

Keywords

Aging; Premature aging; Werner syndrome; NAD(+); Mitophagy; Hallmarkers of aging; DNA repair

Funding

  1. HELSE SoR-OST, Norway [2017056]
  2. Research Council of Norway [262175, 277813]
  3. Hong Kong General Research Fund of the Research Grants Council [14121618]

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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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