TL;DR — InflammagingChronic low-grade inflammation that increases with age and damages tissues silently. Full glossary → is chronic low-grade NF-κB activation without infection. hs-CRP is the accessible anchor (<1.0 mg/L optimal). NRF2 suppresses NF-κB; Zone 2 exercise reprograms myokines; track quarterly labs — models are not substitutes.
What this hallmark means
Inflammaging is persistent, systemic inflammation that rises with age independent of acute infection. It is driven by senescent SASPSenescence-Associated Secretory Phenotype — the inflammatory cocktail of cytokines, proteases, and growth factors secreted by senescent (zombie) cells. Full glossary → secretion, gut barrier leak, visceral adipose IL-6, and inflammasome priming.
| Failure mode | What changes | What you feel |
|---|---|---|
| NF-κB lock-on | Cytokines stay elevated at low amplitude | Stiff joints, brain fog, slow recovery |
| Gut endotoxin translocation | LPS hits TLR4 | Bloating + systemic CRP drift |
| Adipose signaling | Visceral fat acts as endocrine organ | Waist gain correlates with CRP |
Clinically, hs-CRP is the most accessible biomarker: <1.0 mg/L optimal, 1–3 watch, >3.0 elevated cardiovascular risk.
Hallmark 10 · Chronic inflammation
An amplifier — feeds senescence, proteostasis collapse, and mitochondrial ROS. Often the fastest lab to move on TNiC stacks.
Why this matters for your protocol
NRF2A protein that turns on 200+ antioxidant and detox genes when activated. Full glossary → is not only an antioxidant switch — it directly suppresses NF-κB, the master inflammatory transcription factor. That is why the TNiC NRF2 architecture targets inflammaging at signaling level, not symptom management alone.
Intervention hierarchy (evidence-weighted):
- Visceral fat reduction + Zone 2 — strongest mortality-weighted anti-inflammatory signal
- Gut barrier support — fiber, fermented foods, alcohol reduction
- NRF2 stack (GlyNAC + sulforaphane) — gene-level NF-κB counterbalance
- Omega-3 EPA/DHA — specialized pro-resolving mediators (if diet is low)
Sulforaphane activates NRF2 with downstream NF-κB suppression (PMID 38772511). Kumar GlyNAC trials show hs-CRP improvements alongside GSH restoration in older adults.
Practical intervention map
| Lever | Mechanism | Evidence | TNiC resource |
|---|---|---|---|
| Sulforaphane + GlyNAC | NRF2 → NF-κB brake + GSH | Tier A | NRF2 Triad |
| Zone 2 cardio | Myokine IL-6 reprogramming | Tier A | Exercise |
| Sleep | ↓ sympathetic inflammatory tone | Tier A | Sleep |
| Omega-3 | SPM resolution pathways | Tier A | Nutrition |
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Your 90-day inflammaging protocol
Weeks 1–4: Log hs-CRP baseline. Add 150 min/week Zone 2. Remove alcohol if CRP >1.0.
Weeks 5–12: Start GlyNAC 600/600 AM. Retest hs-CRP at week 12.
Weeks 13–24: Add sulforaphane + R-ALA legs per NRF2 triad choreography if CRP still >1.0.
Decision point at week 12: hs-CRP ↓30% → continue. Flat → audit visceral fat, alcohol, sleep before escalating dose.
Which anti-inflammatory path first?
hs-CRP above 1.0 mg/L on two tests 8+ weeks apart?
node | On NSAIDs daily or active autoimmune flare?
redflag | Rheumatologist coordination — NRF2 stack is adjunct only, not replacement
Start GlyNAC → add sulforaphane week 4 → full triad week 8
node | Subjective stiffness/brain fog but CRP <1.0?
Lifestyle sprint 8 weeks (Zone 2 + sleep) → retest CRP
Maintain quarterly CRP surveillance
CRP >10 mg/L or fever — rule out acute infection before longevity protocols
Educational decision aid — a way to organize the evidence, not a prescription. Doses and timing shown are those used in studies; confirm anything you act on with a clinician or pharmacist.
What to measure
| Signal | Type | Frequency | Success looks like |
|---|---|---|---|
| hs-CRP | Lab | Baseline, 12 wk, quarterly | <1.0 mg/L |
| GSH | Lab | Baseline, 12 wk | 5.0+ μmol/L |
| Waist circumference | Anthropometric | Monthly | Trending down if elevated |
| Morning stiffness | Subjective (1–10) | Weekly | ↓2 points |
| Recovery after training | Subjective | Per session | Faster |
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hs-CRP (mg/L)
2.1
GSH (μmol/L)
4.2
Stiffness (1–10)
7
Recovery score
Poor
hs-CRP (mg/L)
0.8
GSH (μmol/L)
5.5+
Stiffness (1–10)
4
Recovery score
Moderate
Red flags — when to pause or escalate
Stop and consult before intensifying
- hs-CRP >10 mg/L — acute infection, autoimmune flare, or occult disease until ruled out
- Autoimmune disease on immunosuppressants — coordinate NRF2/sulforaphane with rheumatologist
- Active IBD flare — sulforaphane GI effects may worsen symptoms
- CRP rising on stack — stop new supplements; physician workup
Synergies worth knowing
| Stack | Covers | Best for |
|---|---|---|
| NRF2 Defense Triad | NF-κB + GSH | Elevated CRP / GSH low |
| NAD+ Mito Stack | Mito ROS → inflammation | Fatigue + CRP borderline |
| Zone 2 + NRF2 | Lifestyle + signaling | Best first-line combo |
Build anti-inflammatory stack
NRF2 preset maps directly to inflammation hallmark coverage.
Open Stack ArchitectPersonal results template
My chronic inflammation log
| Date | Week | hs-CRP | GSH | Stiffness (1–10) | Zone 2 (min) | Alcohol (drinks/wk) | Notes |
|---|---|---|---|---|---|---|---|
| YYYY-MM-DD | 0 | — | — | — | — | — | Baseline |
| YYYY-MM-DD | 12 | — | — | — | — | — | Primary endpoint |
| YYYY-MM-DD | 24 | — | — | — | — | — | Maintenance |
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Personal response criteria: - Meaningful: hs-CRP <1.0 OR ↓30% with stiffness ↓2 points - Plateau: Flat CRP at week 12 → visceral fat + alcohol audit - Adverse: CRP spike or joint swelling → pause stack, physician consult
Further reading
- Franceschi et al. — Inflammaging concept
- Houghton et al. — Sulforaphane NRF2 anti-inflammatory mechanisms
- Kumar GlyNAC trials — GSH, oxidative stressAn imbalance between reactive oxygen species (free radicals) produced by metabolism and the antioxidant systems that neutralize them. Full glossary →, metabolic inflammation
References
- See PMID registry. Sulforaphane upregulates NRF2 and NQO1 in CKD patients. Free Radic Biol Med (2024). PMID 38772511
Links open PubMed. TNiC does not sell supplements; citations support education, not medical advice.