What is inflammaging, how it ages you from within, and science-backed strategies to slow it down. Complete guide with biomarkers, tests and treatments.
Inflammaging is the state of chronic, low-grade inflammation that accompanies aging and accelerates the degeneration of every body system. It produces no obvious symptoms. No pain, no fever. But for years, this persistent immune activation damages blood vessels, neurons, joints and metabolic tissues. Science now considers it one of the primary drivers of accelerated aging and a common denominator across the major chronic diseases of later life.
The term was coined in 2000 by Claudio Franceschi, an immunologist at the University of Bologna, after observing that the healthiest centenarians had significantly lower inflammatory profiles than people in their 70s with chronic disease. His work, expanded in 2018 (Franceschi et al., Nature Reviews Immunology, PMID: 30009220), established inflammaging as a "new immune-metabolic viewpoint" on aging.
Acute vs. chronic inflammation: what makes inflammaging different
Inflammation is not the enemy. It is a defense response that keeps us alive. When you cut yourself, catch an infection or suffer a muscle injury, the immune system activates an inflammatory cascade: specialized cells arrive, local temperature rises, tissues repair. This is acute inflammation. It works, does its job, and shuts off.
The problem is when that alarm signal never fully turns off. Inflammaging is exactly that: a low-intensity, persistent inflammation that doesn't respond to any specific threat but stays on in the background. Like a smoke detector with a dying battery that keeps beeping and nobody listens. Pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) remain chronically elevated. The liver produces more C-reactive protein (CRP) than normal. The activation of NF-κB — the "master switch" of inflammation — never fully turns off.
Senescent cells play a central role. As we age, cells that have suffered irreparable damage accumulate in a state of permanent arrest. These cells don't die: they secrete a cocktail of inflammatory signals called SASP (Senescence-Associated Secretory Phenotype). Each senescent cell acts as a small, continuous fire feeding inflammaging. Yousefzadeh et al. (2018, EBioMedicine, PMID: 30279143) showed that fisetin, a senolytic compound, can eliminate senescent cells and improve health markers and lifespan in animal models.
How inflammaging ages you from within
Inflammaging doesn't target a single system. Its damage is systemic, which explains why the major diseases of old age tend to arrive together.
Cardiovascular disease
Chronic inflammation is the central mechanism of atherosclerosis. It's not simply fats accumulating in arteries: inflammatory processes convert an oxidized LDL particle into an arterial plaque. IL-6 and TNF-α promote adhesion molecule expression on the vascular endothelium, accelerate foam cell formation and destabilize existing plaques. The CANTOS trial (Ridker et al., NEJM, 2017, PMID: 28845751) proved that reducing IL-1β with a monoclonal antibody cut major cardiovascular events by 15%, independent of cholesterol levels. Inflammation is the factor, not just the lipid.
Cognitive decline and Alzheimer's disease
Neuroinflammation — inflammation in the brain — is a determinant factor in Alzheimer's disease and age-related cognitive decline. Microglial cells, which act as the brain's immune system, become chronically activated with inflammaging. They locally generate IL-6 and TNF-α, damage synapses and neurons, and interfere with beta-amyloid clearance. A 2024 longitudinal study in JAMA Network Open found that elevated CRP levels in middle-aged adults were associated with worse declarative memory 10 years later.
Insulin resistance and type 2 diabetes
TNF-α directly interferes with insulin receptor signaling, promoting insulin resistance even without severe obesity. Chronic IL-6 disrupts liver and pancreatic function. Inflammation and metabolic dysfunction feed each other: more visceral fat generates more inflammation, more inflammation promotes more insulin resistance. It's a cycle that accelerates with each passing year.
Sarcopenia and frailty
Chronically elevated TNF-α and IL-6 inhibit muscle protein synthesis and activate degradation pathways like the ubiquitin-proteasome system. The result is progressive loss of muscle mass and strength. Longevity biomarkers like grip strength are partly a proxy for underlying chronic inflammation.
Key inflammaging biomarkers
| Biomarker | What it measures | Optimal range | Elevated risk |
|---|---|---|---|
| hsCRP (high-sensitivity CRP) | General systemic inflammation | < 1.0 mg/L | > 3.0 mg/L |
| IL-6 | Central pro-inflammatory cytokine | < 1.5 pg/mL | > 3.0 pg/mL |
| TNF-α | Chronic immune activation | < 8.1 pg/mL | > 15 pg/mL |
| suPAR | Stable chronic immune activation (more specific than CRP) | Low for age | Correlates with all-cause mortality |
Who is at highest risk?
Inflammaging increases with age in a near-universal pattern. But how fast it progresses depends heavily on lifestyle. Several profiles significantly accelerate the process:
Chronological aging. From around age 40, baseline IL-6 and CRP tend to rise gradually. By age 65, IL-6 levels can be 2-4 times higher than at age 30, even without diagnosed disease (Ferrucci et al., J Gerontol A, 2005). Immunosenescence amplifies the process.
Visceral obesity. Visceral fat tissue is not inert: it acts as an endocrine organ producing pro-inflammatory adipokines (leptin, resistin) while reducing anti-inflammatory ones (adiponectin). People with elevated waist-to-hip ratio have significantly worse inflammatory profiles regardless of BMI.
Physical inactivity. Contracting skeletal muscle produces anti-inflammatory myokines (IL-10, IL-1Ra, post-exercise IL-6 that acts as an anti-inflammatory signal). Without regular exercise, this regulatory capacity is lost. A cohort analysis of over 15,000 adults found that sedentary behavior was associated with CRP levels 40% higher.
Ultra-processed diet. Refined vegetable oils, free sugars, additives and advanced glycation end-products (AGEs) formed during high-temperature cooking are direct inflammatory signals. The typical Western diet chronically activates NLRP3 — a key inflammasome complex.
Chronic stress. Sustained elevated cortisol activates NF-κB and increases pro-inflammatory cytokine production. Chronic psychological stress is associated with IL-6 levels 30-40% higher (Steptoe et al., PNAS, 2007, PMID: 17881589).
Poor sleep. A single night of partial sleep deprivation significantly elevates IL-6 and TNF-α the following day. Chronically short sleep (under 6 hours) is associated with persistently elevated inflammatory profiles.
How to measure your inflammaging
Chronic inflammation produces no symptoms until it has already caused damage. This is exactly why measuring it with biomarkers before disease appears matters.
The basic inflammaging panel includes hsCRP (high-sensitivity CRP, not the standard CRP from a routine blood panel), IL-6, TNF-α and fibrinogen as a cardiovascular risk marker. At Progevita we add suPAR — soluble urokinase plasminogen activator receptor — a biomarker that reflects stable chronic immune activation, less affected by recent acute infections than CRP. suPAR predicts all-cause mortality and correlates with accelerated biological aging (Rasmussen et al., J Gerontol A, 2021, PMID: 32710613).
The next step is connecting these data with epigenetic clocks. Clocks like GrimAge and PhenoAge — developed by researchers at the Harvard Aging Lab (Levine et al., 2018, PMID: 29676998) — integrate inflammation as part of their biological age calculation. GrimAge in particular includes GDF-15 and PAI-1 (which reflect chronic inflammation and vascular dysfunction) in its algorithm. A person with accelerated inflammaging will have a GrimAge significantly older than their chronological age. See our post on longevity biomarkers for a deeper look at epigenetic clocks.
Science-backed strategies to slow inflammaging
The good news: inflammaging is modifiable. With the right interventions, inflammatory cytokine levels can be significantly and sustainably reduced.
Anti-inflammatory nutrition
The Mediterranean diet has the strongest anti-inflammatory evidence base. The PREDIMED trial (Estruch et al., NEJM, 2013) — a randomized controlled trial of 7,447 participants — showed that a Mediterranean diet supplemented with olive oil or nuts reduced cardiovascular events by 30% compared to a low-fat diet. Mechanisms include reductions in IL-6, CRP and ICAM-1. For a detailed implementation guide with a Mediterranean weekly menu, see our evidence-based anti-inflammatory diet guide.
Omega-3 fatty acids (EPA and DHA) inhibit pro-inflammatory eicosanoid synthesis and activate resolvins and protectins — molecules that actively resolve inflammation. Doses of 2-4 g/day of EPA+DHA are associated with 20-25% reductions in IL-6 and TNF-α in meta-analyses. The optimal omega-3 index for longevity is ≥ 8%.
High-glycemic foods activate NLRP3 and elevate protein glycation (AGE formation). Reducing free sugars and refined carbohydrates has a rapid, measurable anti-inflammatory effect within 4-8 weeks.
Exercise: the most potent anti-inflammatory intervention
The combination of strength training + aerobic cardio is more potent than either alone. Muscle gained through resistance training acts as anti-inflammatory endocrine tissue long-term. Zone 2 cardio (60-70% of maximum heart rate) improves mitochondrial function and reduces free radical production, a source of inflammaging. Regular exercise reduces baseline CRP by 20-40% according to a meta-analysis of 33 trials (Hayashino et al., Arch Int Med, 2012).
Sleep: one bad night, one elevated cytokine
A single night of partial sleep deprivation (4 hours) elevates IL-6 and TNF-α the following day in controlled laboratory studies (Vgontzas et al., J Clin Endocrinol Metab, 2004, PMID: 15509641). Deep sleep activates the brain's glymphatic system, which clears beta-amyloid and reduces neuroinflammation.
Stress management: cortisol down, inflammation down
Chronic stress activates the hypothalamic-pituitary-adrenal axis, sustaining elevated cortisol. Chronic cortisol paradoxically desensitizes glucocorticoid receptors on immune cells, reducing their anti-inflammatory effect. The result: higher IL-6 and TNF-α production. Mindfulness-based interventions reduce IL-6 by 15-20% in 8-week clinical trials.
Thermal therapy: hormetic anti-inflammaging signals
Regular sauna use (15-20 minutes, 80-100°C, 4 sessions/week) reduces CRP and increases heat shock protein expression (HSPs), which protect cellular proteins from oxidative damage. A 20-year Finnish follow-up study (Laukkanen et al., JAMA Intern Med, 2015, PMID: 25705824) showed that men using the sauna 4-7 times/week had 63% lower cardiovascular mortality.
Cold exposure — cold showers, ice baths — activates noradrenaline, which has direct anti-inflammatory effects on NF-κB and reduces TNF-α levels.
Medical interventions
When inflammaging is established and biomarkers don't respond to lifestyle changes alone, medical interventions with growing evidence become relevant:
NAD+ therapy. NAD+ levels drop by 50% between ages 40 and 60. NAD+ deficiency impairs sirtuin function — deacetylase proteins that regulate inflammation via NF-κB inhibition — and compromises DNA repair. IV NAD+ infusions rapidly replenish cellular stores with higher bioavailability than the oral route. Read more about NAD+ IV therapy at Progevita.
Ozone therapy. Medical ozone therapy generates a mild, controlled oxidative stress that activates endogenous antioxidant pathways (Nrf2, superoxide dismutase, glutathione peroxidase) and modulates cytokine balance. Major autohemotherapy — blood extraction, ozonation and IV reinfusion — has a documented systemic immunomodulatory effect. At Progevita, ozone therapy is part of the Inflammaging programme under the supervision of Dr. Vivian Borroto, an international specialist in ozone medicine.
Plasmapheresis. Therapeutic plasma exchange physically removes pro-inflammatory proteins, circulating immune complexes, elevated fibrinogen and other inflammaging mediators from the plasma. It is a higher-intensity intervention indicated in established chronic inflammation profiles. Plasmapheresis at Progevita (€1,500) acts as an "inflammatory reset" that potentiates the effect of subsequent interventions.
The future of inflammaging research
Inflammaging research is advancing along several lines that may change available options in the next 5-10 years.
Senolytics. Senolytic drugs selectively eliminate senescent cells feeding the SASP. The dasatinib + quercetin protocol has shown reduction of senescence markers in human tissues in Phase 2 trials (Kirkland & Tchkonia, J Intern Med, 2020). Fisetin, a flavonoid found in strawberries and apples, has shown senolytic properties in murine models (Yousefzadeh et al., 2018). Human trials are ongoing.
Partial cellular reprogramming. Yamanaka factors can "reset" the epigenetic clock of cells without fully dedifferentiating them. Early human studies (Altos Labs, Turn Biotechnologies) are exploring this approach to rejuvenate specific tissues.
NLRP3 inhibitors. The NLRP3 inflammasome is an immune sensor that triggers IL-1β production. It's activated by high glucose, saturated fatty acids, urate crystals and multiple aging signals. Selective NLRP3 inhibitors are in clinical trials for cardiovascular disease, Alzheimer's and gout.
At Progevita, we follow these advances closely while integrating established evidence (nutrition, exercise, biomarkers, ozone therapy, NAD+, plasmapheresis) with continuous learning from emerging clinical trials. To learn how we measure and address inflammaging in our programmes, visit our longevity clinic page or speak directly with our medical team.
Frequently asked questions about inflammaging
Can inflammaging be reversed?
Complete reversal isn't quite the right term, but it can be significantly reduced. With combined interventions (anti-inflammatory diet, regular exercise, quality sleep, stress reduction and, in established cases, medical treatments like NAD+ or ozone therapy), levels of CRP, IL-6 and suPAR can drop to optimal ranges within weeks or months. Eliminating senescent cells via senolytics — the most direct source of SASP — is in active clinical investigation.
At what age does inflammaging start?
It starts in a measurable way around ages 30-35, but the real acceleration occurs from 45-50 onward. Longitudinal studies show that IL-6 and CRP increase gradually from the fourth decade. However, lifestyle influences this so much that a 60-year-old with good habits can have better inflammatory biomarkers than a 40-year-old who is sedentary with a poor diet. Chronological age matters, but biological age is what counts.
Does inflammaging produce symptoms?
Generally, no. That's exactly what makes it dangerous. Chronic fatigue without clear cause, brain fog, slower recovery from exercise, more frequent infections or gradual muscle mass loss can be indirect signals. But in most cases, inflammaging progresses silently until an established disease appears: atherosclerosis, type 2 diabetes, cognitive decline or sarcopenia.
Which tests should I request to detect inflammaging?
The basic panel includes: hsCRP (high-sensitivity, not standard CRP), IL-6, TNF-α, fibrinogen and a differential blood count. For deeper insight: suPAR, ferritin, homocysteine and an epigenetic clock (GrimAge or PhenoAge). At Progevita we include the suPAR test (€99) as part of the Inflammaging programme and as a standalone evaluation.
Can young people be affected by inflammaging?
Yes. Obesity, sedentary behavior, chronic stress, poor sleep and an ultra-processed diet can induce elevated inflammatory profiles in people aged 25-35. A 2023 study in JAMA Cardiology found that 38% of adults aged 18-34 with abdominal obesity had hsCRP levels above 3 mg/L. Inflammaging is not just a question of age.
Scientific references
- Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nature Reviews Immunology. 2018;18(9):576-587. PMID: 30009220.
- Yousefzadeh MJ et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28. PMID: 30279143.
- Ridker PM et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS). NEJM. 2017;377(12):1119-1131. PMID: 28845751.
- Levine ME et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. PMID: 29676998.
- Rasmussen LJH et al. Soluble urokinase plasminogen activator receptor (suPAR) as a predictor of incident disease and mortality. J Gerontol A. 2021;76(10):1738-1749. PMID: 32710613.
- Laukkanen JA et al. Association between sauna bathing and fatal cardiovascular and all-cause mortality events. JAMA Intern Med. 2015;175(4):542-548. PMID: 25705824.
- Vgontzas AN et al. Sleep deprivation effects on sleep physiology and daytime performance. J Clin Endocrinol Metab. 2004;89(3):1351-1361. PMID: 15509641.
- López-Otín C et al. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243-278. PMID: 36599349.
- Estruch R et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet (PREDIMED). NEJM. 2013;368(14):1279-1290. PMID: 23432189.
- Kirkland JL, Tchkonia T. Cellular Senescence: A Translational Perspective. EBioMedicine. 2017;21:21-28. PMID: 28416065.
This article is for informational purposes and does not replace individual medical consultation. Diagnosis and treatment of inflammaging should always be carried out under the supervision of a qualified healthcare professional.
Want to measure your inflammaging level and design a personalised protocol? Talk to our medical team at Balneario de Cofrentes, Valencia — Europe's largest longevity clinic.