What Is NAD+? Its Role in Skin Aging

What Does the Evidence Say?

"NAD+ is a coenzyme that cells use almost like a currency of energy and repair, and its age-related decline is directly linked to a drop in cellular repair capacity."

Looking more closely, NAD+ (Nicotinamide Adenine Dinucleotide) is a molecule that's been known since 1906 but has moved to the center of aging research only in the last decade. Inside the cell it has two core functions: first, acting as an electron carrier in the mitochondrial energy production chain, and second, serving as a cofactor for "NAD+-dependent" enzymes such as sirtuins and PARP. The scientific literature shows that NAD+ levels decline with age across many tissues, including liver, muscle, and fat tissue; one reason for this decline is that the activity of CD38, an enzyme that consumes NAD+, increases with age.^{Camacho-Pereira et al., 2016} The practical takeaway: almost every cell in the body, including skin cells, is increasingly trying to do more with less NAD+ as it ages — laying the groundwork for slower repair and renewal processes.

What Exactly Does NAD+ Do in the Cell?

From Energy Production to Signal Transmission

NAD+'s best-known role is carrying electrons in the mitochondrial ATP (cellular energy) production process; the cycle between NAD+ and its reduced form, NADH, forms the foundation of the cell's energy balance. But NAD+'s function isn't limited to energy production. Similar to Coenzyme Q10's role in the mitochondrial energy chain, NAD+ is also an integral part of cellular energy production — but unlike Coenzyme Q10, NAD+ also behaves like a "signaling molecule." Sirtuins such as SIRT1 require NAD+ directly to function; this family of enzymes is understood to help regulate cellular stress response and mitochondrial health.^{Imai & Guarente, 2014} Another major NAD+ consumer, the enzyme PARP1, activates to repair DNA damage — and in doing so, can rapidly deplete the cell's NAD+ pool.

Why Is NAD+ So Important in Skin Cells?

UV Damage and NAD+ Depletion

Because skin is directly exposed to sunlight, it's especially affected by imbalances in NAD+ metabolism. UV radiation causes DNA damage in keratinocytes; the PARP1 enzyme that activates to repair this damage can sharply lower cellular NAD+ levels.^{Surjana et al., 2013} This can trap skin cells already under pressure from photoaging in a vicious cycle: as NAD+ drops, the cell's repair capacity falls, and as repair capacity falls, accumulated damage increases. Sirtuins' dependence on NAD+ completes this picture — when SIRT1 activity drops, mitochondrial function deteriorates, oxidative stress accumulates, and cellular aging (senescence) can accelerate.

Mitochondrial Health and Visible Aging

Efficient mitochondrial function is critical for energy-intensive processes like collagen production and cell renewal. When NAD+ levels drop, mitochondrial function deteriorates, and this can indirectly affect the overall repair capacity of the skin barrier. In one in vitro study, supplying human fibroblasts with external NAD+ — particularly combined with CD38-inhibiting compounds — was observed to increase cell viability, reduce senescence markers, and limit UV-induced DNA damage.^{Kang et al., 2024} While this finding is promising, it was obtained in a lab setting; whether topical NAD+ application produces the same effect in human skin has not yet been clinically established.

What Do These Signs Mean for You?

Low cellular NAD+ isn't directly visible, but researchers link certain visible signs of aging to a slowdown in NAD+-dependent mechanisms. Here's a summary of the most common signs and their possible connection:

Conclusion

NAD+ is a fundamental coenzyme that plays a role in many critical processes, from energy production and DNA repair to sirtuin activation and mitochondrial health. NAD+ levels that decline with age may indirectly affect skin cells' repair and renewal capacity; however, most of the evidence in this area still comes from laboratory (in vitro) and animal models.

CIRÈLL takes the role of cellular energy metabolism in skin health seriously and follows developments in this field closely, reporting them without exaggeration and faithfully to the original research.

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