Written by the Nuvirox Research Team
Key points
- Inflammaging describes a chronic, low-grade rise in inflammatory signalling with age. IL-6 is the most informative single marker.
- It tracks strongly with frailty, functional decline, and mortality — but association is not the same as cause, and lowering a marker is not the same as improving a life.
- A large meta-analysis found omega-3 and probiotics reduced IL-6 and CRP, while resveratrol and vitamin D did not.
Short answer: inflammaging is a real, measurable drift toward higher inflammatory signalling with age, and it predicts frailty and mortality — but the evidence that lowering it changes outcomes is much thinner than the evidence that it exists. The term describes a state, not a disease. You cannot be diagnosed with it, and the interventions that reliably move its biomarkers are not the ones the supplement industry promotes most heavily.
What does inflammaging actually mean?
Inflammaging refers to a chronic, sterile, low-grade elevation in pro-inflammatory signalling that develops with age in the absence of overt infection. The levels involved are nothing like an acute illness. They are small, persistent shifts — interleukin-6 that would have been essentially undetectable at thirty becoming measurable at seventy.
IL-6 has been described as the single most informative inflammatory marker in older adults for good reason: it rises fairly linearly with age and is repeatedly associated with disability and mortality. C-reactive protein and TNF-alpha follow similar patterns. More recent work has added CXCL9 and composite ratios such as IL-6 to IL-10, on the grounds that inflammatory balance matters more than any single cytokine.
Where does the inflammation come from?
There is no single source, which is part of why it has been hard to treat. The leading contributors are senescent cells, which stop dividing but continue secreting an inflammatory mixture known as the senescence-associated secretory phenotype; visceral adipose tissue, which is metabolically active and inflammatory; a gut barrier that becomes more permeable with age; and accumulated cellular debris that immune surveillance clears less efficiently over time.
This connects directly to NAD+ metabolism. Research in Nature Metabolism showed that senescence-driven inflammation promotes accumulation of CD38-expressing immune cells, and CD38 consumes NAD+. In that model, inflammaging is not merely correlated with NAD+ decline — it drives it.
Does inflammaging cause fatigue?
Partly, and by a route most people find intuitive once it is named. Inflammatory cytokines including IL-6 act on the brain to produce sickness behaviour: reduced motivation, social withdrawal, low energy, and increased sleep pressure. This is a conserved and adaptive response — it is what makes you want to lie down when you have flu, and it is a large part of why fatigue after pneumonia outlasts every other symptom.
The hypothesis is that chronically elevated cytokines produce a low-amplitude, permanent version of the same signal. It is a coherent hypothesis with reasonable supporting evidence. It is not a demonstrated causal chain in humans, and the effect sizes involved are small relative to the effect of, say, untreated sleep apnea. The same neuroinflammatory pathway is invoked to explain why chronic pain is so exhausting.
What human studies actually show
IL-6 predicts mortality and functional decline in large cohorts. The PolSenior study, covering several thousand Eastern Europeans aged 65 and over, found that IL-6 and high-sensitivity CRP were associated with physical and cognitive performance and predicted mortality among people otherwise aging successfully. This is consistent across cohorts.
A composite inflammaging score improved risk prediction beyond frailty. The ReportAGE cohort followed 1,009 hospitalised patients with a median age of 84, combining IL-6, IL-10, and CXCL9 into a single score. The composite added prognostic information beyond a standard deficit-accumulation frailty index. Useful for risk stratification; it does not tell an individual what to do.
The honest counterweight: the intervention meta-analysis was unflattering to popular supplements. Custodero and colleagues systematically reviewed and meta-analysed interventions targeting chronic low-grade inflammation in middle-aged and older adults. Angiotensin receptor blockers, metformin, omega-3 fatty acids, and probiotics significantly reduced IL-6, CRP, or both. Resveratrol and vitamin D — two of the most heavily marketed "anti-inflammatory" supplements — showed no evidence of effectiveness on either marker in the trials conducted to date.
Lifelong exercise helps, but does not reverse the clock. A 2025 systematic review and meta-analysis in Sports Medicine found that lifelong structured exercise was associated with a better inflammatory profile in middle-aged and older adults. It also found that master athletes still showed a more pro-inflammatory profile than untrained young people. Exercise bends the curve; it does not undo age.
Study snapshot
| Study | Custodero et al., Ageing Research Reviews, 2018 |
| Design | Systematic review and meta-analysis of randomized trials |
| Population | Middle-aged and older adults with chronic low-grade inflammation |
| Outcomes | IL-6 and C-reactive protein |
| Result | ARBs, metformin, omega-3 and probiotics reduced markers; resveratrol and vitamin D did not |
What inflammaging won't explain
It will not explain fatigue that started recently. Inflammaging develops over decades. Tiredness that appeared over weeks or months has a different cause, and the list of likely candidates — thyroid disease, iron deficiency, B12 deficiency, sleep apnea, depression, medication side effects — is both longer and more treatable. See a doctor if fatigue is new, progressive, or accompanied by fever, weight loss, night sweats, or joint swelling; those combinations point toward active inflammatory disease rather than background drift.
A raised CRP is not a diagnosis of inflammaging either. CRP rises with infection, injury, obesity, and dozens of conditions. An isolated result without clinical context is not interpretable, which is why most clinicians do not order it as a general screen.
What actually moves the needle
The interventions with the most consistent evidence are unglamorous: regular physical activity, particularly resistance training; reducing visceral fat; adequate sleep, since even short-term sleep restriction raises inflammatory markers; treating existing inflammatory conditions properly; and not smoking. Dietary patterns higher in oily fish and fibre have supporting trial evidence for the marker changes, via omega-3 and the probiotic and microbiome findings respectively.
What is conspicuously absent from that list is most of the supplement aisle. That absence is informative rather than accidental.
Frequently asked questions
Can I get tested for inflammaging?
Not as a defined test. IL-6 and CRP can be measured, but there is no validated threshold that defines inflammaging in an individual, and no treatment decision that follows from the result in an otherwise healthy person.
Is inflammaging the same as autoimmune disease?
No. Autoimmune disease involves the immune system targeting specific tissues, with much higher levels of inflammation and defined diagnostic criteria. Inflammaging is a low-grade, diffuse, sterile elevation without a specific target.
Does an anti-inflammatory diet reverse inflammaging?
It can lower measured markers modestly. Whether that translates into less frailty or longer life has not been demonstrated by randomized trial, which is the honest limit of what can be claimed.
Why do resveratrol and vitamin D show up in every anti-inflammatory list if the meta-analysis found nothing?
Because both have strong mechanistic and preclinical support that has not translated into consistent human biomarker changes. That gap between mechanism and outcome is extremely common in this field and is worth treating as the default expectation.
Does NAD+ supplementation lower inflammation?
The relationship appears to run in the other direction: inflammation drives NAD+ consumption via CD38. Whether raising NAD+ reduces inflammatory markers in humans is a separate question with limited trial data and inconsistent results.
From Nuvirox
Why we formulated NAD+ Restore
NAD+ Restore is formulated around nicotinamide riboside at a dose used in published human trials. We want to be direct about the boundary: it is a cellular health supplement, not an anti-inflammatory treatment.
- 500 mg Nicotinamide Riboside Chloride (NR) — one of the two most-researched NAD+ precursors, within the dose range used in published human trials.
- 150 mg trans-resveratrol (Japanese Knotweed) and 50 mg quercetin (Sophora japonica) — polyphenols studied alongside NAD+ pathways for cellular health support.
- 10 mg galactomannans from fenugreek, to support absorption.
- 60-day money-back guarantee — long enough to actually evaluate it the way the research says you should.
If you have persistently raised inflammatory markers, unexplained fatigue with fever, weight loss, or joint swelling, or a diagnosed inflammatory condition, that needs a doctor's assessment rather than a supplement. Bring the actual results to that appointment.
The bottom line
Inflammaging is one of the better-supported descriptions of what changes with age, and its link to NAD+ consumption via CD38 makes it directly relevant to anyone thinking about cellular energy. What it is not is a condition you can be diagnosed with, monitor usefully at home, or treat with a supplement. The interventions that reliably shifted the biomarkers in randomized trials were exercise, omega-3, probiotics, and metformin — and two of the most heavily marketed anti-inflammatory supplements showed nothing at all.
References
- Custodero C, Mankowski RT, Lee SA, et al. Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: a systematic review and meta-analysis. Ageing Research Reviews. 2018;46:42–59. PMID: 29803716. DOI: 10.1016/j.arr.2018.05.004
- Puzianowska-Kuznicka M, Owczarz M, Wieczorowska-Tobis K, et al. Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study. Immunity & Ageing. 2016;13:21. PMCID: PMC4891873
- Association of an inflammaging score based on IL-6, IL-10 and CXCL9, and frailty with long-term mortality in hospitalized older adults (ReportAGE cohort, n=1,009). Immunity & Ageing. 2025. DOI: 10.1186/s12979-025-00553-5
- Sanchis-Gomar F, et al. Does lifelong exercise counteract low-grade inflammation associated with aging? A systematic review and meta-analysis. Sports Medicine. 2025. DOI: 10.1007/s40279-024-02152-8
- Covarrubias AJ, Kale A, Perrone R, et al. CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. Nature Metabolism. 2020;2:1284–1304. DOI: 10.1038/s42255-020-00298-z
- Camacho-Pereira J, Tarragó MG, Chini CCS, et al. CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metabolism. 2016;23(6):1127–1139. PMID: 27304511. DOI: 10.1016/j.cmet.2016.05.006
- Hogan KA, Chini CCS, Chini EN. The multi-faceted ecto-enzyme CD38: roles in immunomodulation, cancer, aging, and metabolic diseases. Frontiers in Immunology. 2019;10:1187. PMID: 31214171
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This article is for informational purposes only and is not a substitute for professional medical advice.