Inflammaging

What it proposes

Coined by Claudio Franceschi in 2000: aging is fundamentally characterised by a chronic, low-grade, sterile inflammatory state that drives most age-related diseases. Distinguishing features:

• Chronic: persistent for years to decades.
• Low-grade: not the acute-illness range; markers elevated 2–4× baseline rather than 10–100×.
• Sterile: not driven by ongoing infection.
• Systemic: detectable in plasma (IL-6, hsCRP, TNF-α, GDF-15).

Drivers

• Senescent cells secreting SASP factors.
• Damaged mitochondrial DNA activating cGAS–STING.
• Gut microbiome shifts (dysbiosis).
• Visceral adipose tissue as endocrine inflammation source.
• De-repressed retrotransposons.
• NLRP3 inflammasome activation by misfolded proteins, crystals.
• Reduced inflammation-resolution (specialised pro-resolving mediators decline).

Why it’s central

Inflammaging is implicated in:

• Cardiovascular disease.
• Type-2 diabetes.
• Alzheimer’s and other neurodegeneration.
• Sarcopenia and frailty.
• Cancer.
• Bone loss.
• Reduced vaccine responses.

Modifiers

• Exercise: reduces inflammation chronically.
• Mediterranean diet.
• Adequate sleep.
• Weight loss / GLP-1 agonists.
• Senolytics (clear SASP-producing cells).
• Targeted anti-inflammatories: canakinumab (IL-1β), low-dose colchicine, statins.

Related entries

Chronic inflammation, Cellular senescence, hsCRP, IL-6, Immunological theory.