DNA Damage, Metabolism and Aging in Pro-Inflammatory T Cells Rheumatoid Arthritis as a Model System

DNA Damage, Metabolism and Aging in Pro-Inflammatory T Cells Rheumatoid Arthritis as a Model System. Li, Y., Goronzy, J. J., & Weyand, C. M. Experimental gerontology, 105:118–127, May, 2018.

Paper doi abstract bibtex

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 threshold are preserved as long as possible; in maladaptive T cell aging, protective T cell functions decline and proinflammatory 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.

@article{li_dna_2018,
	title = {{DNA} {Damage}, {Metabolism} and {Aging} in {Pro}-{Inflammatory} {T} {Cells} {Rheumatoid} {Arthritis} as a {Model} {System}},
	volume = {105},
	issn = {0531-5565},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871568/},
	doi = {10.1016/j.exger.2017.10.027},
	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 threshold are preserved as long as possible; in maladaptive T cell aging, protective T cell functions decline and proinflammatory 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.},
	urldate = {2019-12-06},
	journal = {Experimental gerontology},
	author = {Li, Yinyin and Goronzy, Jörg J. and Weyand, Cornelia M.},
	month = may,
	year = {2018},
	pmid = {29101015},
	pmcid = {PMC5871568},
	keywords = {ATM, Aging, Arthritis, Rheumatoid, Ataxia Telangiectasia Mutated Proteins, Calcium-Binding Proteins, DNA Damage, DNA Repair, DNA damage responses, DNA-PKcs, Humans, Inflammation, MRE11 Homologue Protein, MRE11A, Rheumatoid arthritis, T cell aging, T-Lymphocytes, Telomere, Telomere Shortening, mtDNA},
	pages = {118--127},
}

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