Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions

Ageing Res Rev. 2017 Jan:33:105-114. doi: 10.1016/j.arr.2016.03.002. Epub 2016 Mar 15.


Werner syndrome (WS) is a prototypical segmental progeroid syndrome characterized by multiple features consistent with accelerated aging. It is caused by null mutations of the WRN gene, which encodes a member of the RECQ family of DNA helicases. A unique feature of the WRN helicase is the presence of an exonuclease domain in its N-terminal region. Biochemical and cell biological studies during the past decade have demonstrated involvements of the WRN protein in multiple DNA transactions, including DNA repair, recombination, replication and transcription. A role of the WRN protein in telomere maintenance could explain many of the WS phenotypes. Recent discoveries of new progeroid loci found in atypical Werner cases continue to support the concept of genomic instability as a major mechanism of biological aging. Based on these biological insights, efforts are underway to develop therapeutic interventions for WS and related progeroid syndromes.

Keywords: Genomic instability; Human; Progeroid syndrome; Werner syndrome.

Publication types

  • Review

MeSH terms

  • Aging, Premature* / genetics
  • Aging, Premature* / metabolism
  • DNA Repair
  • DNA Replication
  • Exodeoxyribonucleases
  • Humans
  • Mutation
  • Werner Syndrome Helicase / genetics*
  • Werner Syndrome* / diagnosis
  • Werner Syndrome* / genetics
  • Werner Syndrome* / metabolism
  • Werner Syndrome* / physiopathology


  • Exodeoxyribonucleases
  • WRN protein, human
  • Werner Syndrome Helicase