Inflammation is a process the body needs. The acute inflammatory response — redness, swelling, the immune system mobilising to a cut or an infection — is one of the oldest and most essential defences in vertebrate biology. The problem is not inflammation as a process. The problem is the chronic, low-grade, systemic version of it that accumulates with age, with no acute trigger, and persists across decades.
This phenomenon now has a name in the longevity literature: inflammaging. The term was coined by Italian immunologist Claudio Franceschi in 2000 and has become one of the most studied concepts in the biology of ageing. Two decades of research have established a robust association between chronic low-grade inflammation and almost every major age-related disease — cardiovascular disease, type 2 diabetes, Alzheimer's, sarcopenia, frailty, and cancer.
What inflammaging actually is
Inflammaging is not a disease state, and it is not the same thing as a chronic inflammatory condition like rheumatoid arthritis. It is a sustained elevation in circulating inflammatory markers — most commonly measured as interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) — without an acute trigger and without producing overt symptoms.
The values involved are modest. Inflammaging does not produce the dramatic elevations seen in active infection or autoimmune flare. Hs-CRP in inflammaging is typically in the 1–3 mg/L range — well below the thresholds clinicians treat in conventional inflammatory disease, but persistently elevated above the 0.5 mg/L benchmark seen in younger, metabolically healthy individuals.
What makes inflammaging consequential is its persistence and its breadth. Acute inflammation lasts hours to days. Inflammaging persists for years. And rather than being targeted at a specific tissue, it is systemic — affecting endothelial function, neuronal signalling, muscle protein synthesis, beta-cell function, and immune surveillance simultaneously.
The mechanism — multiple sources, single effect
One of the reasons inflammaging is hard to address with a single intervention is that it has multiple, partially independent sources. Recent reviews — including a comprehensive 2022 paper in Nature Aging — identify at least six contributing pathways:
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01
Senescent cell accumulation
Cells that have stopped dividing but remain metabolically active accumulate with age. They secrete a cocktail of inflammatory cytokines known as the senescence-associated secretory phenotype (SASP). Even small numbers of senescent cells can produce measurable systemic inflammation.
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02
Gut barrier permeability
"Leaky gut" — the translocation of bacterial products like lipopolysaccharide (LPS) across the intestinal wall into systemic circulation — increases with age, with metabolic dysfunction, and with certain dietary patterns. LPS is a potent activator of the innate immune system.
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03
Visceral adipose tissue
Abdominal fat is a hormonally active organ that secretes pro-inflammatory cytokines. The same kilogram of fat in different locations produces different systemic effects — visceral fat contributes disproportionately to systemic inflammatory signalling.
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04
Mitochondrial dysfunction
Damaged mitochondria release mitochondrial DNA fragments into the cytosol that the innate immune system recognises as pathogen-like. This triggers chronic activation of inflammatory pathways even in the absence of actual infection.
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05
Immunosenescence
The immune system itself ages. The naive T-cell pool contracts, reducing the ability to mount targeted responses, while the innate inflammatory pathways become more easily and persistently activated. The net effect is more background inflammation with less acute responsiveness.
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06
Chronic infection burden
Persistent low-grade infections — particularly cytomegalovirus (CMV), which infects most adults and is never fully cleared — consume immune resources and contribute to chronic activation of inflammatory signalling.
"The unsettling implication of inflammaging research is that the inflammation that ultimately produces age-related disease has often been accumulating, silently, for two to three decades before symptoms appear."
What predicts it — and what shifts it
The lifestyle factors that predict lower inflammaging are largely the same factors that predict longevity more broadly, which is not coincidence. The ones with the strongest evidence base, in approximate order of effect size:
Physical activity. Regular aerobic exercise produces a sustained anti-inflammatory effect via multiple mechanisms — reduced visceral adiposity, improved mitochondrial function, increased anti-inflammatory cytokine production by working muscle (IL-10, IL-1ra). The dose-response relationship is well-established: a 2019 meta-analysis in Brain, Behavior, and Immunity found that 150 minutes of moderate exercise weekly reduced hs-CRP by an average of 0.5 mg/L within 12 weeks of initiation.
Sleep duration consistently in the 7–8 hour range. Chronic sleep restriction below 6 hours nightly produces measurable elevation in IL-6 and TNF-α within a week. This effect is reversible — but only if the sleep deficit is repaired before it becomes a chronic pattern.
Mediterranean-style dietary patterns. The single most studied dietary intervention for inflammaging. The combination of regular consumption of omega-3 rich fish, monounsaturated fats from olive oil, fibre and polyphenols from vegetables, and lower consumption of refined carbohydrates and ultra-processed foods produces consistent reductions in inflammatory marker panels in randomised trials.
Reduction in chronic alcohol intake. Even moderate regular alcohol consumption (above 7 drinks per week) produces measurable elevation in inflammatory markers via direct hepatic effects and via increased gut barrier permeability.
Visceral fat reduction. Because abdominal fat is a major inflammatory source, even modest reductions in visceral adiposity produce disproportionate reductions in systemic inflammatory markers — often visible before significant total weight loss has occurred.
What this means in practice
The unsettling implication of inflammaging research is that the inflammation that ultimately produces clinical disease has often been accumulating, silently, for two to three decades before symptoms appear. The 60-year-old being diagnosed with coronary disease did not develop it in their 50s. The inflammatory signalling that drove the plaque formation began far earlier.
The corollary is also true. The lifestyle inputs that reduce inflammaging are most consequential when applied in the decades preceding the appearance of disease — not as treatments after the fact. The 40-year-old with hs-CRP of 2.5 mg/L is not yet ill. They are accumulating the substrate for future illness, in a quantitatively measurable way, every year that the inflammation persists.
This is not a counsel of alarm. Inflammatory markers are responsive — often within months — to the lifestyle factors that drive them. The biology is plastic in a useful direction, provided the inputs change.