Chronic inflammation and aging: DNA damage tips the balance
Open accessAbstract
The aged immune system, typically hyporesponsive to infection and vaccination, can be hyperresponsive in the context of inflammatory pathology. Here we review current work examining the mechanisms behind the amplified inflammatory profile of aged adaptive immunity, and the reciprocal relationship between chronic inflammation and immune aging. Aged hematopoietic stem cells are driven to differentiate following accumulated DNA damage, thus depleting the stem cell pool and increasing the number of damaged effector cells in the circulation. Chronic DNA damage responses in lymphocytes as well as senescent cells of other lineages initiate the production of inflammatory mediators. In addition, aged lymphocytes become less reliant on specific antigen for stimulation and more prone to activation through innate receptors. When these lymphocytes are exposed to inflammatory signals produced by senescent tissues, the bias toward inflammation exacerbates destruction without necessarily improving immunity.
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- Authors
- Cavanagh, M. M., Weyand, C. M., & Goronzy, J. J.
- Affiliations
- Stanford University (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Goronzy, Jörg J
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 24
- Issue
- 4
- Pages
- 488-493
- ISSN
- 0952-7915 (ISSN-L)
- PMC
- PMC3423478
- OpenAlex
- W1977408830
- Cited by
- 99
- References
- 49
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 15 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 14
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (U19 AI 57266, U19 AI090019, R01 AR42527, R01 EY11916, R01 AI44142, P01 HL058000)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- chronic inflammation, immunosenescence, DNA damage, hematopoietic stem cells, stem cell depletion, lymphocyte senescence, innate immunity, adaptive immunity, inflammatory mediators
- MeSH terms
- Animals, Chronic Disease, DNA Damage, Humans, Immune System, Immunity, Inflammation, Lymphocytes, Cellular Senescence
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