Inflamm-aging does not simply reflect increases in pro-inflammatory markers
Open accessAbstract
Many biodemographic studies use biomarkers of inflammation to understand or predict chronic disease and aging. Inflamm-aging, i.e. chronic low-grade inflammation during aging, is commonly characterized by pro-inflammatory biomarkers. However, most studies use just one marker at a time, sometimes leading to conflicting results due to complex interactions among the markers. A multidimensional approach allows a more robust interpretation of the various relationships between the markers. We applied principal component analysis (PCA) to 19 inflammatory biomarkers from the InCHIANTI study. We identified a clear, stable structure among the markers, with the first axis explaining inflammatory activation (both pro- and anti-inflammatory markers loaded strongly and positively) and the second axis innate immune response. The first but not the second axis was strongly correlated with age (r=0.56, p<0.0001, r=0.08 p=0.053), and both were strongly predictive of mortality (hazard ratios per PCA unit (95% CI): 1.33 (1.16-1.53) and 0.87 (0.76-0.98) respectively) and multiple chronic diseases, but in opposite directions. Both axes were more predictive than any individual markers for baseline chronic diseases and mortality. These results show that PCA can uncover a novel biological structure in the relationships among inflammatory markers, and that key axes of this structure play important roles in chronic disease.
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With a panel of 19 proteins measured in the blood of older adults enrolled in a community-based study, principal component analysis identified two distinct components of immune signaling: a component characterized by simultaneous coexpression of pro- and antiinflammatory proteins that showed a strong positive correlation with age, and a component characterized by an innate immune response that was
“For example, with a panel of 19 proteins measured in the blood of older adults enrolled in a community-based study, Morrisette-Thomas and colleagues used a principal component analysis to identify two distinct components of immune signaling, both of which were associated with current and future chronic age-related disease: (a) a component characterized by simultaneous coexpression of pro- and anti”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [103]
Both components of immune signaling identified by principal component analysis of 19 proteins were associated with current and future chronic age-related disease.
“both of which were associated with current and future chronic age-related disease:”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [103]
A principal component analysis-derived index of pro- and anti-inflammatory markers and innate immune response significantly predicted risk for cardiovascular disease, kidney disease, diabetes, and mortality.
“researchers used principal component analysis to identify pro- and anti-inflammatory markers and an innate immune response that significantly predicted risk for multiple chronic diseases (CVD, kidney disease and diabetes), in addition to mortality51.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [51]
There are no standard biomarkers for chronic inflammatory state, and studies have generally produced conflicting results.
“Despite the importance of this type of inflammatory reaction, there are currently no standard biomarkers to characterize a chronic inflammatory state and studies have generally yielded conflicting results18,19.”
From An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging (2021) · cites this paper as [19]
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- Authors
- Morrisette-Thomas, V., Cohen, A. A., Fülöp, T., Riesco, É., Legault, V., Li, Q., Milot, E., Dusseault-Bélanger, F., & Ferrucci, L.
- Affiliations
- Université de Sherbrooke (CA)
- National Institutes of Health (US)
- Corresponding author
- Cohen, Alan A.
- ORCID
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 139
- Pages
- 49-57
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC5881904
- OpenAlex
- W2081789109
- Cited by
- 283
- References
- 37
- Citations by year
- 2026: 14 · 2025: 31 · 2024: 26 · 2023: 26 · 2022: 33 · 2021: 33 · 2020: 16 · 2019: 27 · 2018: 28 · 2017: 19 · 2016: 17 · 2015: 11 · 2014: 2
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Knowledge UdeS (Institutional Deposit of the University of Sherbrooke) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (Z99 AG999999)
- Canadian Institutes of Health Research (119485, 120305, 110789)
- National Institute on Aging (ZIAAG001050)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- inflammaging, low-grade inflammation, inflammatory markers, principal component analysis, innate immune response, anti-inflammatory markers, mortality prediction, chronic disease, aging, InCHIANTI cohort
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Inflammation, Italy, Male, Middle Aged, Inflammation Mediators
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