Inflammaging — the silent fire of aging

Inflammaging is not simply "too much inflammation." It is an imbalance between the activation, control, and resolution of the immune response.

When we hear the word inflammation, we usually think of infection, fever, redness, pain, or swelling. These are the visible signs of acute inflammation — one of the body's most important survival mechanisms. When we are injured or a microorganism invades the body, the immune system quickly recognizes the problem, organizes a defense, and triggers repair. Such a reaction is usually time-limited.

However, inflammation does not always have to be short-lived, loud, and easily recognizable. The body can harbor long-term, low-grade inflammatory activity without the typical picture of acute infection. When such a pattern develops in the context of aging, scientists call it inflammaging — a term combining the words inflammation and aging, introduced into the scientific literature in the early 2000s by Professor Claudio Franceschi.

Today inflammaging is considered an important meeting point of several aging processes. Still, it is not a separate disease, it is not universally present in every older person, and it cannot be diagnosed with a single laboratory result.

Inflammation is not the enemy

An attempt to reduce every inflammation would be biologically mistaken. Without an inflammatory response the body could not effectively defend against infections, remove damaged cells, or begin wound healing. The problem therefore does not lie in the existence of inflammation itself — the problem arises when the response is excessive, misdirected, active for too long, or when the process of resolving it does not function efficiently enough.

Modern immunology no longer views the end of inflammation as a passive fading of the reaction. Resolution of inflammation is an active, regulated process — the body must stop recruiting new inflammatory cells, remove damaged material, change the signaling environment, and begin tissue repair. If this transition from defense to recovery is not complete, inflammatory signals can remain active far longer than needed.

Why does the inflammatory environment change with age?

Over a lifetime, the body accumulates various forms of damage. DNA undergoes numerous changes, mitochondria become less efficient, damaged proteins are harder to remove, and the capacity for tissue regeneration gradually declines. Cells can recognize such internal damage in a manner similar to external threats — molecules released from damaged cells act as warning signals, which is why inflammaging is often described as sterile inflammation.

At the same time, the immune system itself changes. In part of the older population there is a weaker ability to respond to new infections and vaccines, while certain parts of the innate immune system may remain chronically activated. This combination of immunosenescence and inflammaging can contribute to greater susceptibility to infection, poorer recovery, and chronic disease. Still, the aging of the immune system is not the same in every person.

Senescent cells as a source of signals

When a cell sustains damage it cannot safely repair, it can permanently stop dividing and enter a state of senescence. The problem arises when such cells accumulate excessively over the years and are no longer efficiently cleared by the immune system. Senescent cells can produce cytokines, chemokines, enzymes, and growth factors that alter the behavior of surrounding tissue — a secretory pattern known as SASP.

This creates one of aging's vicious circles: cellular damage promotes inflammation, and chronic inflammation creates the conditions for new damage.

Mitochondria between energy and inflammation

Mitochondria are not just the cell's "power plants" — they also participate in regulating oxidative stress, cell death, and the immune response. When damaged, they can release molecules that resemble bacterial structures, which the immune system recognizes as a danger signal and uses to activate inflammatory pathways. A healthy cell removes damaged mitochondria through a process called mitophagy — if this quality control weakens, nonfunctional mitochondria can accumulate and amplify inflammatory signaling.

Inflammaging does not arise from a single source. It can result from the combined action of mitochondrial dysfunction, cellular senescence, DNA damage, impaired autophagy, metabolic disturbance, and changes in the microbiome.

Visceral fat tissue is not a passive reserve

Fat tissue was long viewed merely as a storage site for excess energy. We now know it is metabolically and endocrinologically active. Visceral fat tissue, located around the internal organs, is particularly important — when it expands excessively, fat cells can become functionally overloaded and produce larger amounts of pro-inflammatory signals.

For this reason, central obesity is closely linked to insulin resistance, fatty liver disease, dyslipidemia, and increased cardiovascular risk. Still, waist circumference alone is not proof of inflammaging — it gains clinical meaning only when linked to blood pressure, glycemia, lipids, and other risk factors.

The gut barrier and the microbiome

The gut microbiome participates in breaking down food, producing metabolites, and regulating the local immune response. With age, illness, dietary changes, and medication use, changes can occur in the microbiome and in gut-barrier function, making it easier for microbial components to come into contact with the immune system and trigger inflammatory signals. The relationship is bidirectional — chronic inflammation also alters conditions in the gut.

The popular claim that "all disease begins in the gut" is not medically justified. The gut may be one source of inflammatory burden, but it is not the only one — infections, periodontal disease, fat tissue, autoimmune diseases, sleep disorders, and smoking can also affect inflammatory status.

From the blood vessel to the brain

Chronic inflammation appears in the biology of a large number of age-related diseases, but its role is not identical in each of them. Atherosclerosis is not merely passive deposition of cholesterol in the arterial wall — the retention of ApoB-containing lipoproteins and the response of immune cells together contribute to the formation and progression of plaque. In type 2 diabetes, inflammatory signals from fat tissue, the liver, and immune cells can contribute to insulin resistance.

In the brain, activation of microglia and other forms of neuroinflammation participate in the response to damage, but Alzheimer's disease is not simply "inflammation of the brain." In osteoarthritis, mechanical load, cartilage changes, and local inflammatory signaling act together. The same applies to malignant disease — biology requires balance, not complete shutdown of the immune system.

Does inflammaging have symptoms?

Inflammaging has no specific set of symptoms on which a diagnosis can be based. Fatigue, sleep disturbance, pain, reduced concentration, and slower recovery are often attributed to chronic inflammation, but the same complaints can result from anemia, thyroid dysfunction, sleep apnea, depression, or numerous other conditions.

One person may have elevated inflammatory markers without pronounced symptoms, while another may have numerous complaints with entirely normal standard indicators. The first step must always be clinical assessment, aimed at recognizing or ruling out a specific disease requiring treatment.

What can the laboratory actually show us?

C-reactive protein is an acute-phase protein produced by the liver under the influence of inflammatory signals. Standard CRP is used to assess more pronounced inflammation, while high-sensitivity hs-CRP can measure much lower concentrations and has a confirmed role in assessing cardiovascular risk in appropriately selected patients — but it is not specific to aging and does not indicate the source of inflammation.

Interleukin-6 and TNF-alpha are of great importance in inflammaging research but are not routine screening tests for healthy people. Erythrocyte sedimentation rate, fibrinogen, ferritin, and other parameters can contribute to assessment in a particular clinical context, but none of them alone diagnoses inflammaging. There is no single "test for inflammaging" — assessment arises from linking history, examination, risk factors, and carefully chosen laboratory findings.

Genetics does not measure current inflammation

Genetic variants in genes involved in regulating cytokines and the immune response can influence individual differences in inflammatory reactivity. Still, the presence of a particular polymorphism in genes such as CRP, IL6, IL6R, or TNF does not mean a person currently has chronic inflammation — the genetic result does not reveal the intensity of the process, its source, or its clinical consequences.

Genetics can therefore describe part of a predisposition, but it cannot replace measurement of current health status. It has the greatest value when interpreted in the context of family history, confirmed risk factors, and the question the test is meant to answer.

Functional medicine and the search for the source

One of the appealing ideas of functional medicine is the search for factors that sustain chronic inflammatory activity. Such an approach can be useful when clinically disciplined — it requires considering body composition, metabolic health, sleep, physical activity, diet, and possible infections.

The problem arises when every vague complaint is automatically attributed to inflammation, gut permeability, or cortisol without appropriate diagnostics. The goal is not to find as many potential "sources of inflammation" as possible — the goal is to distinguish a relevant signal from laboratory noise and identify a factor on which we can act safely and with evidence.

Can we reduce inflammaging?

There is no single intervention that completely eliminates inflammaging, but there are several ways to reduce inflammatory and metabolic burden.

• Regular physical activity — appropriately dosed exercise is associated in the long term with a more favorable metabolic and inflammatory profile.
• Reducing excess visceral fat tissue, without aggressive weight loss in older individuals.
• A Mediterranean dietary pattern — more minimally processed plant foods, adequate protein, olive oil, and fish.
• Quality sleep — obstructive sleep apnea requires particular attention.
• Smoking cessation, rational alcohol use, and treatment of periodontal disease.

This is not a single "anti-inflammatory therapy." It is an integrated strategy for preserving health.

Why one capsule is not the answer

The supplement market often uses the term inflammation because it is broad enough to be linked to almost any health problem. Polyphenols, omega-3 fatty acids, curcumin, and numerous other substances are studied in the context of inflammatory pathways, but a change in a single biomarker does not prove that a supplement has slowed aging or prevented disease.

The effect depends on baseline nutritional status, product quality, dose, and health condition — interactions and adverse effects are possible. One must first determine whether a concrete problem exists, whether the intervention has proven benefit, and how its effect will be monitored.

New science seeks a more precise inflammaging

Modern research increasingly avoids trying to describe inflammaging with a single average marker. Inflammatory profiles differ among people — in one person the dominant burden may come from visceral fat tissue, in another from chronic disease, and in a third from repeated infections or sleep disorders. The future likely does not belong to a single diagnosis of "inflammaging," but to more precise recognition of individual immunometabolic patterns and their sources.

Conclusion

A single symptom does not prove inflammaging. A single marker does not reveal its source. A single supplement does not resolve a complex biological network.

Inflammaging describes chronic, low-grade inflammatory activity that develops with aging in some people and is associated with a greater risk of chronic disease. It is not an infection, it is not a separate diagnosis, and it is not simple proof that the body is "burning from within." It represents a meeting point of cellular senescence, mitochondrial dysfunction, metabolic burden, microbiome changes, and altered regulation of the immune system.

Inflammation can simultaneously protect and cause harm. Its complete suppression is not the goal — the goal is to restore the body's ability to activate an inflammatory response when needed, control its intensity, and end it once the danger has passed.

AFLM — from inflammatory marker to clinical context

The Academy for Functional and Longevity Medicine develops an approach in which inflammation is not viewed as an isolated laboratory value. Our goal is for health professionals to understand the biology of the inflammatory response, recognize the limitations of tests, and link results to history, examination, and a concrete clinical decision.

Knowledge before technology.
The clinical question before the test.
The patient before the result.

Sources

• Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: A New Immune–Metabolic Viewpoint for Age-Related Diseases. Nature Reviews Endocrinology. 2018.
• Ferrucci L, Fabbri E. Inflammageing: Chronic Inflammation in Ageing, Cardiovascular Disease, and Frailty. Nature Reviews Cardiology. 2018.
• Baechle JJ, Chen N, Makhijani P, et al. Chronic Inflammation and the Hallmarks of Aging. Molecular Metabolism. 2023.
• López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of Aging: An Expanding Universe. Cell. 2023.
• Franceschi C, et al. Toward Precision Interventions and Metrics of Inflammaging. 2025.

Note: This text is educational in nature and does not constitute individual medical advice. Persistently elevated inflammatory markers or unexplained symptoms require medical evaluation. Medications and supplements should not be started or stopped based solely on an assumption about inflammaging.