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

23 Scopus citations


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
StatePublished - May 2018


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

ASJC Scopus subject areas

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


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