Hallmark #10 of 12
Inflammaging — the silent accelerator
"Inflammaging" — the slow-burning systemic inflammation that accumulates with age — predicts cardiovascular events, cancer risk, and cognitive decline more reliably than almost any other single biomarker.
Chronic Inflammation
hs-CRP above 1 mg/L doubles 10-year cardiovascular risk; above 3 mg/L it triples — and ∼40% of "healthy" adults over 50 are in this range. Inflammaging drives every other hallmark: it shortens telomeres via ROS, silences PGC-1α to suppress mitochondrial biogenesis, exhausts stem niches via IL-6 and p38-MAPK, and accelerates the epigenetic clock via DNMT3A recruitment. The practical first-order priority is fixing hs-CRP — targeting sulforaphane + GlyNAC + omega-3 together addresses NF-κB, GSH-IKKβ, and SPM resolution arms simultaneously.
4 compound interventions · 4 trackable biomarkers
Top interventions
- ASulforaphane (NRF2 anti-inflammatory)
- AGlyNAC (glutathione / ROS)
- BResveratrol (NF-κB / SIRT1)
- AOmega-3 (EPA+DHA)
- AZone 2 + resistance exercise
The Mechanism
NF-κB — the master inflammatory switch of aging
Inflammaging has five converging sources. SASP from senescent cells is the largest — secreting IL-6, IL-1β, and TNF-α continuously into surrounding tissue. Gut permeability allows bacterial LPS to enter circulation, triggering TLR4/NF-κB. Mitochondrial ROS activate the NLRP3 inflammasome, producing IL-1β. Immune senescence (exhausted T-cells, skewed macrophages) impairs resolution. Visceral adipose acts as a SASP-like endocrine organ.
The convergence point is NF-κB. It integrates all these signals and transcribes the inflammatory gene program: COX-2 (prostaglandins), iNOS (nitric oxide), IL-6, IL-1β, TNF-α, and MMP-3/9 (ECM-degrading). Targeting NF-κB upstream — via NRF2, SIRT1, or SPM precursors — is more durable than targeting individual cytokines downstream.
hs-CRP is the clinical readout. C-reactive protein is produced by the liver in response to IL-6 — making it a downstream integrator of systemic NF-κB activity. Values above 3.0 mg/L independently predict cardiovascular events (JUPITER trial), all-cause mortality (Ridker et al.), and accelerated cognitive decline.
The good news: inflammaging is highly modifiable. Omega-3 index moving from 4% to 8% reduces hs-CRP ~30%. Sulforaphane reduces CRP in human airway models within 4 weeks. Exercise training reduces hs-CRP ~20% in sedentary adults at 3 months. The TNiC stack targets NF-κB from three independent angles — NRF2 (upstream ROS), SIRT1 (direct NF-κB deacetylation), and SPM precursors (active resolution).
Monitoring
Inflammaging biomarker panel
Log hs-CRP, IL-6, and homocysteine in the Lab Tracker to monitor trend over time.
Evidence-Graded Interventions
Anti-inflammaging interventions with human evidence
Sulforaphane (NRF2 anti-inflammatory)
Tier ASuppresses NF-κB via NRF2-ARE pathway. Reduces CRP in human airway studies.
GlyNAC (glutathione / ROS)
Tier AReduces oxidative drivers of inflammation. Human trials show improved inflammatory markers.
Resveratrol (NF-κB / SIRT1)
Tier BModulates inflammatory gene expression via SIRT1 deacetylation of NF-κB subunits.
Omega-3 (EPA+DHA)
Tier AEPA/DHA generate resolvins, protectins, and maresins — specialized pro-resolving mediators that actively terminate inflammation. REDUCE-IT trial: 4g/day EPA reduced cardiovascular events 25% (PMID 30145934). Meta-analysis: significant hs-CRP and IL-6 reduction.
Zone 2 + resistance exercise
Tier AMyokines (IL-6 transient, IL-10 sustained) reprogram immune tone with training.
Extinguish inflammaging.
Build a multi-angle NF-κB suppression protocol: NRF2 + SIRT1 + omega-3. Track hs-CRP quarterly in the Lab Tracker.