Inflammaging

Inflammaging, a term coined by Claudio Franceschi in the early 2000s, describes the chronic, low-grade, sterile inflammatory state that develops with age, driven by senescent cell secretions (SASP), declining immune regulation, and accumulated cellular debris [1]. Unlike acute infection-driven inflammation, inflammaging persists at a low level for years and is measured with blood markers including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and high-sensitivity C-reactive protein (hs-CRP) [1].

Large population studies consistently link higher IL-6 and hs-CRP with increased risk of cardiovascular disease, frailty, and all-cause mortality in older adults; a 2018 review found IL-6 to be among the most reliable single predictors of mortality and disability in aging cohorts, outperforming several other inflammatory markers in head-to-head comparisons [2]. A 2023 Nature Reviews Endocrinology paper reframed inflammaging as an "immune-metabolic" phenomenon, linking it mechanistically to obesity, insulin resistance, and gut microbiome changes rather than treating it as a purely immunological process [3].

What the evidence does not show: while inflammatory markers predict risk, no anti-inflammatory drug trial designed specifically to reduce inflammaging (as opposed to treating a specific inflammatory disease) has shown it extends healthy lifespan in a large human RCT. The CANTOS trial, which tested the anti-inflammatory drug canakinumab in people with prior heart attacks and elevated hs-CRP, reduced cardiovascular events (hazard ratio roughly 0.85 for the primary endpoint) but also increased fatal infection rates compared with placebo, illustrating that suppressing inflammation broadly carries real trade-offs rather than being a free intervention [5].

Bryan Johnson's Blueprint protocol tracks hs-CRP closely as a primary inflammation marker; he has publicly reported an hs-CRP of 0.1 mg/L, which he describes as 66% below the average level in a 10-year-old, an n=1 self-reported outcome from his diet, exercise, and supplement regimen rather than a controlled comparison [4].

Critics note that inflammatory markers are non-specific: hs-CRP rises with infection, injury, obesity, and periodontal disease as much as with underlying aging biology, so a single low reading does not prove reduced biological aging, only the absence of detectable current inflammation [3]. The hallmarks-of-aging framework treats chronic inflammation as its own dedicated hallmark as of the 2023 update, reflecting how central the concept has become to the broader aging-biology literature rather than remaining a narrower immunology topic [6].

The plain takeaway: inflammaging is a well-supported and clinically useful concept for risk prediction, but treating the inflammation itself, rather than its upstream drivers, has produced mixed results in trials.