Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging
Abstract
Innate and adaptive immunity are the major defence mechanisms of higher organisms against inherent and environmental threats. Innate immunity is present already in unicellular organisms but evolution has added novel adaptive immune mechanisms to the defence armament. Interestingly, during aging, adaptive immunity significantly declines, a phenomenon called immunosenescence, whereas innate immunity seems to be activated which induces a characteristic pro-inflammatory profile. This process is called inflamm-aging. The recognition and signaling mechanisms involved in innate immunity have been conserved during evolution. The master regulator of the innate immunity is the NF-kB system, an ancient signaling pathway found in both insects and vertebrates. The NF-kB system is in the nodal point linking together the pathogenic assault signals and cellular danger signals and then organizing the cellular resistance. Recent studies have revealed that SIRT1 (Sir2 homolog) and FoxO (DAF-16), the key regulators of aging in budding yeast and Caenorhabditis elegans models, regulate the efficiency of NF-kB signaling and the level of inflammatory responses. We will review the role of innate immunity signaling in the aging process and examine the function of NF-kB system in the organization of defence mechanisms and in addition, its interactions with the protein products of several gerontogenes. Our conclusion is that NF-kB signaling seems to be the culprit of inflamm-aging, since this signaling system integrates the intracellular regulation of immune responses in both aging and age-related diseases.
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Basal inflammageing is driven by NF-κB signaling and generally renders immune cells initially hyporesponsive to acute activation, with the possible exception of monocyte subsets.
“Basal inflammageing is driven by NF-κB signaling and generally renders immune cells initially hyporesponsive to acute activation, with the possible exception of the monocyte subsets71,81.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [71]
NF-κB is regulated by cytokines, growth factors, SIRT1, SIRT6, and FOXO.
“NF-κB is regulated by many upstream factors and regulators including cytokines, growth factors, the deacetylases SIRT1 and SIRT6, and the transcription factor FOXO (Kawahara et al., 2009; Salminen et al., 2008).”
From The Aging Epigenome (2016) · cites this paper as Salminen et al., 2008
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- Authors
- Salminen, A., Huuskonen, J., Ojala, J., Kauppinen, A., Kaarniranta, K., & Suuronen, T.
- Affiliations
- University of Eastern Finland (FI)
- Corresponding author
- Salminen, Antero
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 7
- Issue
- 2
- Pages
- 83-105
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W1981477005
- Cited by
- 581
- References
- 28
- Citations by year
- 2026: 24 · 2025: 38 · 2024: 41 · 2023: 39 · 2022: 43 · 2021: 48 · 2020: 40 · 2019: 43 · 2018: 24 · 2017: 30 · 2016: 26 · 2015: 21 · 2014: 33 · 2013: 35 · 2012: 20
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- inflammaging, innate immunity, NF-κB signaling, immunosenescence, aging, SIRT1, FOXO, DAF-16, age-related diseases, innate immune signaling, immune system evolution
- MeSH terms
- Aging, Animals, Humans, Immunity, Innate, Inflammation, Models, Biological, Signal Transduction, NF-kappa B
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