Longevity
6 min read•Archived in NAD_Research_Packet.pdf & Dallas2.json
The Inflammaging Cascade: How Depleted Sirtuins Accelerate Chronic Disease
As NAD+ declines, sirtuins lose the substrate needed to suppress NF-κB, igniting a chronic low-grade inflammatory fire that depletes remaining NAD+ in a destructive loop.
“As NAD+ declines, the body's ability to neutralize inflammation is compromised. Inflammation causes further cellular damage, which demands more NAD+ for repair, further depleting supply.”
— Dr. Fenton LeBon, MD, MBA
Core Scientific Takeaways
- Inflammaging is the chronic, sterile, low-grade systemic inflammation that characterizes aging.
- SIRT1 normally suppresses inflammatory cytokines by deacetylating the NF-κB p65 subunit.
- Without adequate NAD+, NF-κB hyperactivates, releasing IL-6, TNF-α, and MMP enzymes.
- Tissue damage recruits PARP and CD38, draining remaining NAD+.