NMN and the Immune System: Why NAD+ Matters for Immunity Over 40

Immune Health Guide · Updated June 2026

After 40, many Australians notice a pattern: colds that used to last three days now last seven. Recovery from any illness — or even just a demanding week — takes longer. The immune system's responsiveness, its capacity to resolve challenges quickly and return to baseline, has become less reliable.

This is not simply bad luck. It reflects a well-documented phenomenon called immunosenescence — the age-related decline of immune function — which is mechanistically connected to NAD+ depletion through several specific pathways.

How NAD+ Connects to Immune Function

Immune cell energy metabolism: Immune cells — particularly T cells and natural killer (NK) cells — undergo rapid proliferation when responding to a pathogen. This proliferation is metabolically intensive and requires efficient mitochondrial ATP production. NAD+ depletion reduces immune cell energy efficiency, potentially impairing the speed and magnitude of immune responses.

SIRT1 and immune regulation: SIRT1 — activated by NAD+ — regulates the expression of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β through NF-κB modulation. When SIRT1 activity declines from NAD+ depletion, inflammatory gene expression becomes less tightly regulated — contributing to the chronic, low-grade inflammation (inflammaging) that characterises immune ageing.

CD38 and immune NAD+ consumption: CD38 — the NAD+-consuming enzyme that increases with age and inflammation — is highly expressed on immune cells. The more active and inflamed the immune system, the more CD38 activity, the more NAD+ consumed. This creates a feedback loop: age-related immune dysregulation increases CD38, which depletes NAD+, which impairs SIRT1-mediated immune regulation, which worsens inflammation.

What Is Inflammaging?

Inflammaging is the term for the chronic, low-grade inflammatory state that develops with age — distinct from acute inflammation that resolves after a challenge. Unlike the sharp inflammatory response to a pathogen that peaks and clears, inflammaging is a persistent background inflammation driven by:

• Senescent cell SASP output — ongoing inflammatory signalling from accumulated zombie cells
• Reduced SIRT1-mediated anti-inflammatory regulation from NAD+ depletion
• Accumulated cellular debris from impaired autophagy
• Gut microbiome changes that increase circulating bacterial products

Inflammaging is associated with virtually every age-related disease — cardiovascular disease, metabolic syndrome, cognitive decline, and cancer risk all increase with higher inflammatory burden. It is not a minor background issue — it is one of the primary drivers of why health deteriorates with age.

What NMN and Quercetin Address in Immune Ageing

NMN → NAD+ → SIRT1: Restoring NAD+ supports SIRT1 activity in immune cells — helping regulate inflammatory gene expression and reduce the chronic inflammatory output of dysregulated immune signalling. This addresses the NAD+-SIRT1-NF-κB axis of inflammaging directly.

Quercetin → senolytic clearance + direct anti-inflammatory: Quercetin clears senescent cells that are producing the SASP inflammatory output driving inflammaging. It also directly inhibits NF-κB and COX-2 — reducing inflammatory mediator production independently of the senolytic effect. For the immune component of ageing, Quercetin is the most directly evidence-supported ingredient in the formula.

What the Evidence Shows — Honestly

No human RCT has demonstrated that NMN reduces infection frequency or directly improves immune response to pathogens. The benefit pathway is indirect: reducing the chronic inflammatory burden that dysregulates immune function, and supporting immune cell energy metabolism that may enable more efficient responses.

The Quercetin evidence for inflammaging reduction in humans is stronger — multiple studies document reduction in inflammatory markers (CRP, IL-6) from Quercetin supplementation. For the immune ageing component specifically, Quercetin is the most evidence-supported element of Nadovia's formula.

FAQ

References: Franceschi C et al., Nat Rev Immunol (2018) — inflammaging; Camacho-Pereira J et al., Cell Metabolism (2016) — CD38; Quercetin anti-inflammatory human studies. Not medical advice.