DNA damage, metabolism and aging in pro-inflammatory T cells: Rheumatoid arthritis as a model system

Yinyin Li, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations

Abstract

The aging process is the major driver of morbidity and mortality, steeply increasing the risk to succumb to cancer, cardiovascular disease, infection and neurodegeneration. Inflammation is a common denominator in age-related pathologies, identifying the immune system as a gatekeeper in aging overall. Among immune cells, T cells are long-lived and exposed to intense replication pressure, making them sensitive to aging-related abnormalities. In successful T cell aging, numbers of naïve cells, repertoire diversity and activation thresholds are preserved as long as possible; in maladaptive T cell aging, protective T cell functions decline and pro-inflammatory effector cells are enriched. Here, we review in the model system of rheumatoid arthritis (RA) how maladaptive T cell aging renders the host susceptible to chronic, tissue-damaging inflammation. In T cells from RA patients, known to be about 20 years pre-aged, three interconnected functional domains are altered: DNA damage repair, metabolic activity generating energy and biosynthetic precursor molecules, and shaping of plasma membranes to promote T cell motility. In each of these domains, key molecules and pathways have now been identified, including the glycolytic enzymes PFKFB3 and G6PD; the DNA repair molecules ATM, DNA-PKcs and MRE11A; and the podosome marker protein TKS5. Some of these molecules may help in defining targetable pathways to slow the T cell aging process.

Original languageEnglish (US)
Pages (from-to)118-127
Number of pages10
JournalExperimental Gerontology
Volume105
DOIs
StatePublished - May 2018

Keywords

  • ATM
  • DNA damage responses
  • DNA-PKcs
  • Inflammation
  • MRE11A
  • mtDNA
  • Rheumatoid arthritis
  • T cell aging
  • Telomere

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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