Evidence note · Immune ageing and glycan biology
Inflammaging: The Hidden Link Between Chronic Inflammation, Immune Ageing and the Hallmarks of Ageing
Why chronic low-grade inflammation connects ageing, immune dysfunction and age-related disease, and what emerging glycan biomarkers can and cannot yet tell us about it.
- Published
- Author
- Bettina van Wylich-Muxoll
- Reading time
- 8 min
Ageing is not simply the passage of time
Two individuals of the same chronological age can have profoundly different biological profiles. One may retain metabolic flexibility, immune resilience and functional capacity, while the other develops chronic inflammation and declining physiological reserve.
Chronic low-grade inflammation, termed inflammaging by Franceschi and colleagues in 2000, is a persistent inflammatory state that becomes more prevalent with advancing age, even without overt infection. It is not a disease in itself, nor can it be adequately described by a single inflammatory biomarker. It reflects interactions among immune regulation, cellular damage, metabolic signalling and tissue homeostasis.
Inflammaging and the 12 Hallmarks of Ageing
In 2023, López-Otín and colleagues expanded the framework of ageing biology to twelve interconnected hallmarks. Chronic inflammation, previously grouped under altered intercellular communication, became a hallmark in its own right. The twelve are: genomic instability; telomere attrition; epigenetic alterations; loss of proteostasis; disabled macroautophagy; deregulated nutrient-sensing; mitochondrial dysfunction; cellular senescence; stem cell exhaustion; altered intercellular communication; chronic inflammation; and dysbiosis.
These processes interact. Senescent cells may develop a senescence-associated secretory phenotype (SASP), releasing inflammatory mediators. Inflammatory signalling can influence mitochondrial function, tissue repair and immune behaviour. Gut microbiome changes may also affect host-microbial signalling and systemic inflammation. Biological ageing can promote inflammation, while persistent inflammation may reinforce ageing-related mechanisms.
Why the immune system changes with age
Immunosenescence refers to age-associated changes in immune-cell composition and function; inflammaging refers to persistent low-grade inflammatory activity. They frequently coexist but are not interchangeable.
Ageing can affect innate immune signalling, lymphocyte diversity, tissue immune surveillance and inflammatory resolution. Persistent inflammation is associated with cardiovascular disease, metabolic dysfunction, frailty and neurodegenerative conditions. For cardiovascular disease, there is also interventional evidence: in the CANTOS trial, targeting interleukin-1β reduced recurrent cardiovascular events independently of cholesterol lowering. Even so, inflammation is one contributor among many, not the sole cause of age-related disease.
Beyond CRP: can we measure immune-related biological ageing?
C-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) can inform assessments of inflammatory activity, but none comprehensively describes immune ageing. CRP also rises with infection, injury and other physiological stressors, so a single value reflects the moment of the draw.
IgG glycosylation offers a complementary molecular perspective. Rather than measuring only the concentration of inflammatory proteins, it characterises carbohydrate structures attached to antibodies. These structures can influence immune function and vary with age and inflammatory states.
The science of IgG glycosylation
Immunoglobulin G (IgG), the most abundant antibody class in serum, carries carbohydrate structures called glycans. The conserved N-linked glycan at asparagine 297 in the Fc region affects how antibodies interact with Fcγ receptors and complement components.
With age, in population studies
- Galactosylation↓ Lower with age
- Agalactosylation (G0)↑ Higher with age
- Sialylation↓ Often lower
- Bisecting GlcNAc↑ May increase
- GlcNAc
- Mannose
- Galactose
- Sialic acid
- Fucose
Population studies commonly report lower IgG galactosylation and higher agalactosylation with age; sialylation often decreases and bisecting GlcNAc may increase. These are population patterns, not universal individual trajectories. Functional effects depend on antibody subclass, antigen specificity and biological context.
Glycosylation is also shaped by factors other than age. It is partly heritable, and genetics, hormones, environment and disease all influence it. Sex hormones matter in particular: oestrogen is associated with higher galactosylation, and women’s profiles often shift around the menopausal transition. Sex-specific interpretation is therefore important.
Biological age is not the same as immune age
DNA methylation clocks, proteomic models, metabolomic approaches and IgG glycan-based models measure different biological features, and their estimates often disagree for the same person. An IgG glycan-derived age estimate is a model-based representation of age-associated glycosylation patterns. It is not a direct measurement of total-body biological age, immune competence or disease risk, and it is not a summary of overall health.
One person, chronological age 50 · illustrative values
- DNA methylation clockChemical marks on DNA
- Proteomic modelProtein abundance
- Metabolomic modelSmall molecules in blood
- IgG glycan modelSugar chains on antibodies
Interpretation should consider the underlying molecular pattern, the reference population and relevant confounders. Glycan-age models have been developed largely in European-ancestry cohorts, so applicability to other populations should not be assumed. Results may also be harder to interpret during pregnancy, acute infection, or active inflammatory or autoimmune disease.
Can immune-related biological ageing change?
Longitudinal studies indicate that IgG glycosylation is not static. Research has linked weight change and the menopausal transition with shifts in glycan profiles. Intervention studies of testosterone, metformin and calorie restriction have reported mixed, population-dependent findings.
Most of the evidence base is observational; interventional studies are fewer and still developing. These findings show that glycosylation responds to physiological change. They do not establish that lowering a glycan-derived age score reverses ageing, improves clinical outcomes or extends healthspan.
From a single measurement to longitudinal insight
Three different questions decide whether a change in a result means anything:
| Question | What it asks |
|---|---|
| Analytical reliability | Do equivalent samples give consistent results? |
| Biological variability | How much does a person’s profile fluctuate naturally with hormones, illness, medication or season? |
| Clinical meaningfulness | Does a change predict better health or function? |
A laboratory’s within-day (in-day) precision describes repeat measurement of the same sample in one run. It does not capture between-run variation or a person’s own biological fluctuation, and both matter when comparing tests months apart. For individual monitoring, reference change values, minimum detectable changes, appropriate retesting intervals and outcome validation are needed. A measurable shift is not necessarily a clinically meaningful improvement.
About the Immune Ageing & Glycan Biology test
BioAgeDiagnostics’ Immune Ageing & Glycan Biology test is performed by our accredited laboratory partner. It analyses age-associated IgG glycosylation patterns and is offered as a complementary perspective alongside other measures, not a replacement for them.
| Feature | Detail |
|---|---|
| Laboratory | CLIA-certified partner laboratory |
| Sample | Finger-prick dried blood spot |
| Analysis | IgG N-glycan profiling, samples run in triplicate |
| Analytical precision | ±1 year within-day (in-day) precision, as reported by the laboratory |
| Report | Glycan-derived age estimate plus five glycan indexes of pro- and anti-inflammatory glycans |
| Turnaround | 3–4 weeks |
The test addresses one biological layer: antibody glycosylation and immune-related ageing patterns. Other layers include DNA methylation, protein abundance, metabolic state, established clinical biomarkers and physiological function. More measurements do not automatically improve decisions; added value requires validation and appropriate interpretation.
Intended use. The test is a supplementary marker of immune-related ageing patterns for research-informed health assessment. It is not a diagnostic test, does not predict individual lifespan or specific disease, and is not intended to guide medication dosing.
What should clinicians consider before using glycan biomarkers?
Clinical integration should distinguish three things:
- Analytical validity: the marker is measured reliably.
- Clinical validity: it is meaningfully associated with relevant outcomes.
- Clinical utility: using the result improves decisions or outcomes.
IgG glycosylation is biologically relevant, but evidence for guiding individual treatment remains immature. Glycan-derived age estimates should not independently diagnose disease, determine or titrate treatment (including hormone therapy or weight-loss medication), or be used to show that an intervention has reversed ageing. Treatment decisions should rest on established clinical criteria, with glycan results interpreted as supplementary information.
The future: from association to actionable biology
The next frontier is not simply more sophisticated clocks, but knowing which biomarkers provide reproducible and clinically meaningful information. Four questions matter. Does a biomarker identify differences beyond age and conventional risk factors? Does it remain reliable across populations and repeated measures? Do changes predict improved health or function? Does measuring it improve outcomes?
Conclusion: understanding inflammation is part of understanding ageing
Inflammaging links immune-related inflammation with interconnected biological processes of ageing. IgG glycosylation offers a promising molecular perspective because antibody glycans are involved in immune regulation and show age-associated patterns.
At BioAgeDiagnostics, the objective is not simply to generate another biological age number. It is to understand how biological systems change over time, and to establish which of those changes matter for long-term health.
Scientific references
- Franceschi C, et al. Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–254. doi:10.1111/j.1749-6632.2000.tb06651.x
- López-Otín C, et al. Hallmarks of aging: an expanding universe. Cell. 2023;186:243–278. doi:10.1016/j.cell.2022.11.001
- Baechle JJ, et al. Chronic inflammation and the hallmarks of aging. Mol Metab. 2023;74:101755. doi:10.1016/j.molmet.2023.101755
- Ridker PM, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease (CANTOS). N Engl J Med. 2017;377:1119–1131. doi:10.1056/NEJMoa1707914
- Krištić J, et al. Glycans are a novel biomarker of chronological and biological ages. J Gerontol A Biol Sci Med Sci. 2014;69:779–789. doi:10.1093/gerona/glt190
- Immunoglobulin G glycosylation and its alterations in aging-related diseases. 2024. PubMed 39126246
- Immunoglobulin G glycans — biomarkers and molecular effectors of aging. Clin Chim Acta. 2022. doi:10.1016/j.cca.2022.08.006
- High-throughput N-glycan analysis in aging and inflammaging. 2024. PubMed 39383621
- Glycan clock of ageing — analytical precision and time-dependent variability. 2024. PMC11494675
- The importance of IgG glycosylation — what did we learn after analyzing over 100,000 individuals. 2024. PMC11659926
- Vinicki M, et al. Effects of testosterone and metformin on the GlycanAge index. GeroScience. 2025. PubMed 39363095
- A 2-year calorie restriction intervention may reduce glycomic biological age biomarkers. npj Aging. 2025. doi:10.1038/s41514-025-00254-9
Disclosure and regulatory note
Disclosure. BioAgeDiagnostics offers the Immune Ageing & Glycan Biology test in partnership with an accredited laboratory, which performs the analysis.
Regulatory note. This article is intended for professional education and general health information. IgG glycan-derived age estimates are emerging biomarkers. They are not established diagnostic tools for inflammatory disease or immune dysfunction, and they are not validated for guiding individual treatment or medication dosing.
Questions
What is inflammaging?
Chronic low-grade inflammation, termed inflammaging by Franceschi and colleagues in 2000, is a persistent inflammatory state that becomes more prevalent with advancing age, even without overt infection. It is not a disease in itself, nor can it be adequately described by a single inflammatory biomarker.
Is inflammaging one of the Hallmarks of Ageing?
Yes. In 2023, López-Otín and colleagues expanded the framework of ageing biology to twelve interconnected hallmarks. Chronic inflammation, previously grouped under altered intercellular communication, became a hallmark in its own right.
What is the difference between immunosenescence and inflammaging?
Immunosenescence refers to age-associated changes in immune-cell composition and function; inflammaging refers to persistent low-grade inflammatory activity. They frequently coexist but are not interchangeable.
What does IgG glycosylation tell us about immune ageing?
Rather than measuring only the concentration of inflammatory proteins, it characterises carbohydrate structures attached to antibodies. These structures can influence immune function and vary with age and inflammatory states. An IgG glycan-derived age estimate is a model-based representation of age-associated glycosylation patterns. It is not a direct measurement of total-body biological age, immune competence or disease risk.
Can a glycan-derived age score be lowered?
Longitudinal studies indicate that IgG glycosylation is not static, and intervention studies have reported mixed, population-dependent findings. These findings show that glycosylation responds to physiological change. They do not establish that lowering a glycan-derived age score reverses ageing, improves clinical outcomes or extends healthspan.