There is a phenomenon in ageing biology that has acquired a specific term because it is so ubiquitous and so consequential: inflammaging. Coined by the Italian immunologist Claudio Franceschi, the term describes the chronic, low-grade, systemic inflammation that characterises the ageing process and that serves as the biological substrate for virtually every major age-related disease. It is not the acute inflammation of a healing wound or a responding immune system. It is a persistent, low-level inflammatory state that smoulders for decades, gradually damaging tissues, impairing cellular function, and accelerating the biological decline that produces frailty, disease, and premature death. The good news, if it deserves that description, is that inflammaging is substantially driven by modifiable factors and is measurable with standard laboratory tests.
The Biology of Inflammaging
The primary sources of chronic low-grade inflammation in the ageing body are visceral adipose tissue, which functions as an endocrine organ releasing pro-inflammatory cytokines including interleukin-6, interleukin-1 beta and tumour necrosis factor alpha; cellular senescence, whereby old damaged cells that refuse to die instead secrete a cocktail of inflammatory molecules called the senescence-associated secretory phenotype; age-related changes in the gut microbiome that allow bacterial endotoxins to leak into the bloodstream and trigger immune activation; and the progressive loss of regulatory T-cells that normally dampen immune responses. Each of these processes feeds the others, creating a self-reinforcing cycle. Visceral fat promotes cellular senescence; senescent cells release cytokines that promote further fat accumulation and gut permeability; gut permeability increases endotoxin exposure that triggers further immune activation.
The clinical consequences of inflammaging extend across every major disease category. CRP, a marker of systemic inflammation, predicts cardiovascular events independently of cholesterol. IL-6, produced by visceral fat and senescent cells, predicts type 2 diabetes onset years before the metabolic condition appears on standard tests. Chronic neuroinflammation, driven partly by peripheral inflammatory cytokines crossing the blood-brain barrier, is increasingly identified as a driver of Alzheimer's disease pathology rather than merely a consequence of it. In cancer biology, the tumour microenvironment relies on chronic inflammation to suppress immune surveillance and promote angiogenesis. The 2020 Lancet Commission on dementia prevention identified chronic inflammation as one of twelve modifiable risk factors for dementia; but the same mechanisms are implicated in most of the other eleven.
What Drives Inflammaging in Practical Terms
Understanding the drivers of inflammaging makes intervention straightforward in principle, even if the execution requires sustained effort. Excess visceral adipose tissue is the single most modifiable driver. A reduction of even five to ten percent of body weight in adults with abdominal obesity produces measurable reductions in CRP, IL-6, and TNF-alpha within twelve weeks. Poor sleep is a powerful driver, with even one night of partial sleep deprivation producing measurable inflammatory cytokine elevations; chronic sleep restriction under six hours is associated with CRP levels twice as high as those seen in adults sleeping seven to eight hours. Ultra-processed food diets drive inflammaging through multiple pathways: refined carbohydrate promotes glycation and advanced glycation end-products; seed oils high in omega-6 fatty acids shift the eicosanoid balance towards pro-inflammatory prostaglandins; additives and emulsifiers in ultra-processed food disrupt gut barrier function.
Smoking, alcohol excess, sedentary behaviour, and psychological stress are additional modifiable drivers, each with documented inflammatory consequences. Chronic psychological stress activates the HPA axis, elevating cortisol and adrenaline, which initially suppress inflammation but, with prolonged activation, lead to glucocorticoid receptor resistance and paradoxical immune upregulation. The social isolation that often accompanies loneliness has also been shown in prospective data to predict elevated inflammatory markers, suggesting that the social determinants of health operate partly through inflammatory mechanisms. The implication for clinical practice is that reducing inflammaging requires a multi-domain intervention addressing body composition, sleep, diet quality, movement, stress and social connection simultaneously, not sequentially.
The Most Evidence-Supported Anti-Inflammatory Interventions
The Mediterranean dietary pattern, characterised by high olive oil, fish, vegetables, legumes, whole grains, and nuts with low red meat and ultra-processed food, reduces CRP by approximately 20 percent in randomised trials and is the most consistently replicated dietary intervention for reducing inflammatory markers. Omega-3 fatty acids, whether from oily fish or high-quality supplementation, reduce the synthesis of pro-inflammatory eicosanoids and produce measurable CRP reductions at doses of two to four grams of EPA plus DHA daily. Resistance training reduces visceral adiposity and senescent cell burden while upregulating anti-inflammatory myokines including IL-6 during exercise and IL-15 chronically; the acute IL-6 release during muscle contraction has opposite effects to the chronic low-grade IL-6 of visceral fat. Time-restricted eating reduces inflammatory markers in clinical trials, partly through its effects on visceral fat and partly through circadian alignment of immune function.
For adults on the Isle of Man presenting to Zhen Wellness with elevated inflammatory markers, the clinical approach is to identify the primary drivers for that individual using body composition assessment, dietary analysis, sleep quality evaluation and lifestyle assessment, and to sequence interventions accordingly. The sequence matters because some interventions are prerequisite for others: improving sleep quality makes dietary change easier; reducing visceral fat improves sleep quality; exercise improves both. The Longevity MOT provides the baseline data needed to identify which driver is most prominent and therefore where to start.
- Inflammaging is a chronic low-grade inflammatory state that underpins cardiovascular disease, type 2 diabetes, dementia and cancer
- Primary drivers are visceral fat, cellular senescence, gut permeability and impaired regulatory T-cell function
- Visceral fat reduction of 5 to 10 percent reduces CRP, IL-6 and TNF-alpha within 12 weeks
- Chronic sleep under 6 hours doubles CRP levels compared with 7 to 8 hours sleep
- The Mediterranean diet reduces CRP by approximately 20 percent in randomised trials
- Resistance training reduces visceral fat and senescent cell burden while upregulating anti-inflammatory myokines
- Multi-domain intervention addressing body composition, sleep, diet and movement is more effective than single-domain approaches
Sources
- Franceschi, C., et al. (2000). Inflamm-aging: an evolutionary perspective on immunosenescence. Annals of the New York Academy of Sciences, 908(1), 244-254.
- Ridker, P.M., et al. (2017). Antiinflammatory therapy with canakinumab for atherosclerotic disease. New England Journal of Medicine, 377(12), 1119-1131.
- Irwin, M.R., & Opp, M.R. (2017). Sleep health: reciprocal regulation of sleep and innate immunity. Neuropsychopharmacology, 42(1), 129-155.
- Calder, P.C. (2013). Omega-3 polyunsaturated fatty acids and inflammatory processes. Biochemical Society Transactions, 41(1), 269-276.
- Livingston, G., et al. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet, 396(10248), 413-446.