Inflammation, Glycans & Aging Biology

Explanation of the relationship between inflammatory signaling, antibody glycosylation, and the biological aging process, focusing on the mechanisms that shape long-term health and disease risk.

How does inflammation drive biological aging?

Chronic, low-grade inflammation can accelerate biological aging by increasing cellular stress, disrupting tissue repair, and reshaping immune function over time. These changes promote many downstream aging mechanisms (including metabolic dysfunction and immune dysregulation) and are consistently linked to higher risk of age-related disease in population studies.

Inflammation is essential for healing, but when inflammatory signaling stays mildly elevated for years it can become damaging. Age-related drivers include accumulated cellular debris, senescent-cell signaling, changes in gut microbiota, and nutrient-related metabolic inflammation. This persistent inflammatory background is strongly associated with common age-related conditions, and many “biological age” models either directly include inflammatory markers or reflect pathways influenced by inflammation. Importantly, inflammation can be both a contributor to aging biology and a consequence of underlying disease processes—so it’s best interpreted as a systems-level signal, not a single-cause explanation.

What is inflammaging?

Inflammaging is the chronic, typically “sterile” (non-infectious), low-grade inflammation that becomes more common with aging. It reflects long-term immune activation from multiple sources and is linked to higher vulnerability to many age-related diseases, without being specific to any one condition.

The term was introduced to describe how older adults often show modestly elevated inflammatory signaling even without acute infection. Proposed contributors include lifelong immune stimulation, senescent-cell inflammatory secretions, metabolic inflammation related to adiposity and diet, and shifts in gut microbiota. Inflammaging is best understood as an “environment” that increases risk and reduces resilience, rather than a diagnosis. Because many diseases also raise inflammation, the presence of inflammaging signals should prompt broader clinical and lifestyle context rather than condition-specific conclusions.

What biomarkers best measure chronic inflammation?

No single biomarker perfectly captures chronic inflammation. The most commonly used measures include high-sensitivity CRP (hs-CRP), IL-6, TNF-α, and fibrinogen, often interpreted together. Composite measures like GlycA can reflect broader inflammatory protein activity and may be more stable than single markers in some settings.

hs-CRP is widely available and useful for tracking systemic inflammatory burden, but it can rise transiently with infection or injury. Cytokines such as IL-6 and TNF-α are biologically informative but can be more variable and assay-dependent. Evidence suggests inflammatory biomarkers show better stability over shorter intervals and may require repeat measurement for chronic assessment. GlycA is an NMR-derived composite signal linked to chronic inflammation and future risk in large cohorts, making it a useful complement when available. Best practice is trend-based interpretation and avoidance of single time-point overreach.

What is IgG glycosylation?

IgG glycosylation is the pattern of sugar chains attached to IgG antibodies. These sugars act like “dials” that tune how strongly IgG triggers inflammatory immune responses. Certain glycan features are associated with more pro-inflammatory or more anti-inflammatory antibody behavior, and they shift with age and health.

IgG antibodies have a region (the Fc) that communicates with immune cells. Sugars attached to this region change how well IgG engages immune receptors and activates downstream inflammatory pathways. For example, changes in galactosylation and sialylation are repeatedly discussed as functionally important for inflammatory “tone.” Because these glycan patterns respond to immune and metabolic signaling over time, they can function as integrated markers of immune aging—capturing longer-term biology rather than moment-to-moment fluctuations.

Why do glycans change before disease develops?

Glycans can shift before clinical disease because glycosylation responds to early, preclinical changes in immune regulation, inflammation, and metabolism. In some longitudinal research settings, IgG glycosylation differences have been observed years before disease onset, suggesting glycans can act as early risk-related biomarkers, not diagnoses.

Many chronic diseases develop gradually, with immune and metabolic changes emerging long before symptoms or diagnosis thresholds. Because glycosylation is enzymatically regulated and sensitive to the body’s inflammatory and metabolic environment, IgG glycan patterns can reflect this “pre-disease” biology. Longitudinal cohort findings show associations between IgG glycan traits and incident outcomes in certain conditions, supporting the idea that glycan shifts may precede clinically recognized disease in some contexts. The correct interpretation is probabilistic: a pattern can resemble those seen before disease in populations, but it cannot confirm that disease is present in an individual.

Does fasting reduce inflammation?

Fasting can reduce some inflammatory markers in some people, but results are mixed and often depend on weight loss, baseline metabolic health, and the fasting approach. Calorie restriction has more consistent evidence for lowering CRP and IL-6 in overweight/obesity trials than intermittent fasting. Prolonged fasts (≥48 hours) may temporarily increase inflammatory markers in several studies.

In randomized-trial meta-analyses in overweight/obesity, calorie restriction shows measurable reductions in CRP (and sometimes IL-6), while intermittent fasting has fewer trials and less consistent biomarker effects. Time-restricted eating meta-analyses suggest small reductions in TNF-α and leptin, with less consistent effects on CRP and IL-6. Separately, reviews of prolonged fasting report that CRP and other inflammatory markers often rise during the fasting period, with variable responses after refeeding. Practically, fasting is best framed as a strategy that may improve inflammation indirectly through fat loss and metabolic improvements, rather than a guaranteed direct anti-inflammatory intervention.

Scope disclaimer: This content is for educational purposes only and does not constitute a medical diagnosis or treatment guide.

Scientific grounding: This information is aligned with findings from peer-reviewed research in the fields of aging biology and molecular biomarkers.

GlycanAge provides biological age testing to help individuals monitor their immune health and chronic inflammation patterns over time.