Chronic inflammation and immune-mediated processes are pivotal to the pathogenic progression of multiple age-related diseases, such as cardiovascular disease (CVD), cancer, age-related macular degeneration (AMD), Alzheimer’s disease and, and type II diabetes. This chronic low-grade inflammatory status associated with ageing, named “inflammaging” plays a role in the emergence and progression of such age-related disorders. Indeed, increased levels of systemic acute-phase reactants represent a risk factor for age-related diseases.
C-reactive protein (CRP) is the prototypical acute-phase reactant and an active regulator of the innate immune system. It is considered to be a serum biomarker for chronic inflammation, CVD, diabetes, Alzheimer, and also AMD. Increased CRP levels are also associated with more severe forms of the new COVID19, where age is considered the main risk factor for poor outcome. CRP localizes to damaged tissue where it leads to complement activation and further tissue damage. Indeed, it has been identified in vascular, cerebral and ocular lesions, but little is known about its function in the context of disease onset and progression in inflammaging. Besides activating the classical complement pathway, CRP up-regulates the expression of adhesion molecules, and increases cytokine release from endothelial cells, neutrophils and macrophages. In plasma, CRP typically exists as a cyclic pentamer (pCRP) composed of five non-covalently linked subunits. However, pCRP can undergo dissociation into its monomeric subunits, thereby acquiring distinct biological functionality. Oxidative stress and bioactive lipids from activated or damaged cells present during inflammatory responses can dissociate pCRP. This alternative conformation of CRP termed monomeric CRP (mCRP) represents the tissue-based insoluble form of CRP and unlike pCRP, it displays a proinflammatory and prothrombotic phenotype in several cell types. Indeed, recent evidence suggests that mCRP may be an active player in the progression of age-related diseases such as cardiovascular disorders, Alzheimer, and AMD. A better understanding of the CRP activation and dissociation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Therefore, reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of age-related disorders. One of the major focuses of this second series is therapeutic translation and the possible role of C-reactive protein monitoring and manipulation in disease pathogenesis and particularly in age-related disorders.
Despite the recognition of the importance of chronic inflammation in age-related pathologies, the role of acute-phase reactants and the mechanisms underlying the inflammatory regulation in these disorders are not fully understood.
This Research Topic will cover a wide range of subjects in CRP and acute-phase reactants in chronic inflammation and age-related diseases. Original Research, Review, Mini Review, Perspective, Commentary, and Opinion articles are welcome to this Research Topic. Potential topics include, but are not limited to:
1. Mechanisms regulating inflammation in age-related diseases.
2. The role of CRP and acute phase reactants in age-related diseases.
3. CRP-mediated inflammation and signaling pathways.
4. Inflammatory markers and CRP in the diagnosis of age-related disorders.
5. Chronic inflammation in age-related diseases (Alzheimer, cardiovascular diseases, age-related macular degeneration, type II diabetes, cancer, etc).
6. CRP and inflammaging.
7. CRP in COVID-19 and other viral conditions.
8. Meta-analysis and bioinformatics on CRP.
9. Genetics and epigenetics studies on CRP.
10. CRP in cancer.
This Research Topic is the third volume of the “Community Series in C-Reactive Protein in Age-Related Disorders”. Please see the first volume
here, and the second volume
here.