What Is NAD+? Benefits, How It Works, and How to Boost It

NAD+ has become one of the most talked-about molecules in longevity science — and for good reason. But what actually is it, and why should you care about it? Here’s the clearest explanation of NAD+, what it does, and why its decline with age is so significant.

What Is NAD+?

NAD+ stands for nicotinamide adenine dinucleotide — a coenzyme found in every living cell in your body. It is one of the most abundant molecules in biology and is involved in over 500 enzymatic reactions. Think of it as a fundamental currency of cellular metabolism and cellular health maintenance.

NAD+ exists in two main forms in the body: NAD+ (the oxidised form) and NADH (the reduced form). The cycling between these two forms drives energy production in the mitochondria and powers the reactions that keep cells alive and functional.

What Does NAD+ Do?

1. Energy Production

NAD+ is essential for the Krebs cycle and oxidative phosphorylation — the cellular processes that produce ATP (adenosine triphosphate), your cells’ primary energy currency. Without NAD+, mitochondria cannot generate energy efficiently. This is directly relevant to why NAD+ decline is associated with fatigue, reduced physical performance, and metabolic slowdown in ageing.

2. Sirtuin Activation

Sirtuins are a family of proteins (SIRT1–SIRT7) often called longevity genes — they regulate gene expression, DNA repair, inflammation control, and metabolic health. Critically, sirtuins require NAD+ to function. Without adequate NAD+, sirtuins are inactive regardless of how healthy your diet or lifestyle is. When David Sinclair and others talk about activating sirtuins through caloric restriction, exercise, or resveratrol — all of these effects require sufficient NAD+ to work.

3. DNA Repair

PARP enzymes (poly ADP-ribose polymerases) detect and repair DNA damage — the daily accumulation of breaks and mutations in your DNA from oxidative stress, UV radiation, and metabolic byproducts. PARPs are voracious consumers of NAD+; when DNA damage is high (as in ageing, illness, or UV exposure), PARP activity can deplete NAD+ rapidly, creating a vicious cycle where low NAD+ means poor DNA repair, which means more DNA damage, which depletes more NAD+.

4. Immune Function and Inflammation

CD38 — an enzyme on immune cells — is also a major consumer of NAD+. During infection or chronic inflammation, CD38 activity increases dramatically, consuming NAD+ and contributing to the NAD+ decline associated with chronic inflammatory conditions. This is one reason chronic inflammation and ageing compound each other so effectively.

Why NAD+ Declines With Age

NAD+ levels decline by approximately 50% between ages 40 and 60 in most tissues. This is driven by:

• Increased PARP activity (more DNA damage to repair)
• Increased CD38 activity (chronic low-grade inflammation of ageing — “inflammageing”)
• Reduced NAD+ biosynthesis (the salvage pathway becomes less efficient)
• Reduced dietary precursor intake (most diets are poor in tryptophan-rich foods that feed the de novo synthesis pathway)

This decline is not trivial. Lower NAD+ means less efficient energy production, impaired DNA repair, reduced sirtuin activity, and compromised cellular stress response — all hallmarks of biological ageing.

How to Boost NAD+ Levels

Frequently Asked Questions

This article is for informational purposes only. Consult a healthcare provider before starting NAD+ precursor supplementation.

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Related reading: NAD+ and Longevity, Longevity Supplements, What Is Spermidine?, Autophagy and Aging.