Cold‐inflammaging: When a state of homeostatic‐imbalance associated with aging precedes the low‐grade pro‐inflammatory‐state (inflammaging): Meaning, evolution, inflammaging phenotypes
Abstract
The age‐related pro‐inflammatory state, discovered and called ‘inflammaging’ by Franceschi et al. (2000) plays an important role in the pathogenesis of age‐related chronic diseases. A substantial body of data established that inflammaging is accompanied by a ‘2‐fold to 4‐fold’ increase in plasma levels of pro‐inflammatory mediators in healthy elderly people, when compared to the healthy adult population. This review focuses on the pre‐inflammaging phase, here we reported as ‘cold‐inflammaging’, a state where plasma levels of cytokines are slightly increased, but below the lower limit of 2‐fold increase established for inflammaging. Slightly altered cytokine levels by innate immunity are known to be associated with homeostasis imbalances, this functional pleiotropy of cytokines as signal transducers, have a physiological counterpart, representing an adaptive process aimed at restoring (or achieving a new) homeostatic stability. If a dyshomeostatic state persists, the cytokine response by innate immunity increases and becomes a driver of inflammaging. A scenario where cytokines are characterised as major players in homeostasis imbalances at the beginning (cold‐inflammaging) and then in chronic low‐grade pro‐inflammatory‐state (inflammaging). Other important drivers of inflammaging are cellular senescence with its senescence‐associated secretory phenotype, the altered gut microbiota, and the age‐related dysregulation in the production of endogenous molecular waste (Garb‐aging). The main purpose of this review being to thoroughly investigate each step of the pathway from cold‐inflammaging to overt‐inflammaging, because aging, cold‐inflammaging, overt‐inflammaging and the pathogenesis of age‐related diseases have been shown to share some established basic pillars of geroscience that largely converge on inflammaging.
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Inflammaging develops from cold-inflammaging with a less than 2-fold increase of pro-inflammatory mediators in plasma compared to healthy adults.
“Inflammaging develops from cold-inflammaging with a less than 2-fold increase of pro-inflammatory mediators in plasma, compared to healthy adults.200”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [200]
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Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
- Authors
- Giunta, S., Wei, Y., Xu, K., & Xia, S.
- Affiliations
- Casa di Cura Prof. Nobili–GHC Garofalo Health Care Bologna Italy
- Fudan University (CN)
- Corresponding author
- Xia, Shijin
- Venue
- Clinical and Experimental Pharmacology and Physiology
- Publisher
- Wiley
- Published
- 2022-07-04
- Volume
- 49
- Issue
- 9
- Pages
- 925-934
- ISSN
- 0305-1870 (ISSN-L)
- 1440-1681
- OpenAlex
- W4281761884
- Cited by
- 27
- References
- 60
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 2 · 2023: 4 · 2022: 2
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Experimental Pharmacology and Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81870044)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- inflammaging, low-grade inflammation, homeostatic imbalance, cytokines, innate immunity, cellular senescence, senescence-associated secretory phenotype, gut microbiota, age-related chronic diseases, geroscience
- MeSH terms
- Aging, Homeostasis, Humans, Inflammation, Phenotype, Cytokines
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