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DNA damage, metabolism and aging in pro-inflammatory T cells
- Source :
- Experimental Gerontology. 105:118-127
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
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 naive 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 20years 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.
- Subjects :
- 0301 basic medicine
Aging
Podosome
DNA damage
Effector
DNA repair
T cell
Inflammation
Cell Biology
Biology
Biochemistry
Cell biology
Telomere
03 medical and health sciences
030104 developmental biology
Endocrinology
Immune system
medicine.anatomical_structure
Immunology
Genetics
medicine
medicine.symptom
Molecular Biology
Subjects
Details
- ISSN :
- 05315565
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Experimental Gerontology
- Accession number :
- edsair.doi...........63e1d51e10256786f3785bfc9c38921b