Telomere dysfunction, autoimmunity and aging

Philipp J. Hohensinner, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations

Abstract

Immune aging is associated with loss of critical immune functions, such as host protection from infection and malignancy. Unexpectedly, immunosenescence also renders the host susceptible to inflammation, which may translate into tissue-damaging disease as the senescent immune system loses its ability to maximize inflammatory protection while minimizing inflammatory injury. On the other hand, chronic inflammation associated with immune-mediated disease represents a profound stress factor for the immune system, affecting cellular turn-over, replication and exhaustion. Immune cell longevity is tightly connected to the functional integrity of telomeres which are regulated by cell multiplication, exposure to oxidative stress and DNA repair mechanisms. Lymphocytes are amongst the few cell types that can actively elongate telomeres through the action of telomerase. In patients with the autoimmune disease rheumatoid arthritis (RA), telomerase deficiency is associated with prematurity of immune aging. Patients with RA have other defects in DNA repair mechanisms, including the kinase Ataxia telangiectasia mutated (ATM), critically involved in the repair of DNA double strand breaks. ATM deficiency in RA shortens lymphocyte survival. Dynamics of telomeric length and structure are beginning to be understood and have distinct patterns in different autoimmune diseases, suggesting a multitude of molecular mechanisms defining the interface between chronic immune stimulation and progressive aging of the immune system.

Original languageEnglish (US)
Pages (from-to)524-537
Number of pages14
JournalAging and Disease
Volume2
Issue number6
StatePublished - 2011

Keywords

  • Autoimmunity
  • Diabetes
  • Lupus
  • Rheumatoid arthritis
  • Sarcoidosis
  • Shelterin
  • Telomerase
  • Telomere
  • Telomere dysfunction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cell Biology

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