New Approach to Skin Anti-Aging with NAD⁺

Nicotinamide adenine dinucleotide (NAD⁺) is an indispensable small molecule in cellular metabolism, driving energy production, DNA repair, epigenetic regulation and other vital processes. Its intracellular concentration declines with age and is implicated in multiple age-related disorders. Replenishing NAD⁺ or its precursors is therefore viewed as a strategy to delay—or even reverse—aging.

A recent study by a Korean team has developed a method that markedly amplifies the anti-aging effect of exogenous NAD⁺ on skin by improving its bioavailability through targeted inhibition of CD38, the main NAD⁺-degrading enzyme.

1. CD38 inhibition elevates intracellular NAD⁺

Exogenous NAD⁺ can be taken up by cells but simultaneously induces CD38 expression, leading to rapid NAD⁺ breakdown. Co-treatment with quercetin plus enoxolone (glycyrrhetinic acid) synergistically suppresses CD38 expression, more than doubling intracellular NAD⁺ levels.

2. Mechanistic validation of anti-aging effects

Photo-aging model (UV-irradiated fibroblasts):

• NAD⁺ + inhibitor cocktail markedly reduces senescence markers (p16, p21, MMP-1).

• DNA damage (γH2AX foci and comet-tail moment) is significantly diminished.

• Cellular senescence rates fall while overall viability rises.

Intrinsic aging model (replicative senescence):

• Population-doubling capacity of dermal fibroblasts is extended.

• Longevity-associated Sirtuins are activated.
• Autophagy flux is enhanced.

• Mitochondrial function improves, evidenced by higher ATP output, increased membrane potential and reduced oxidative stress.

3. Anti-inflammatory action

In LPS-stimulated RAW264.7 macrophages, the NAD⁺ + inhibitor combination suppresses the production of NO, TNF-α, IL-1β and IL-6, suggesting potential mitigation of inflammaging.

4. Wound-healing promotion

Under NAD⁺-depleted conditions (induced by FK866), the same combination accelerates fibroblast migration and proliferation while up-regulating wound-repair genes such as Ki67, COL3A1 and TGF-β.

This work is the first systematic demonstration that exogenous NAD⁺ exerts robust anti-aging effects in human dermal fibroblasts. By co-administering quercetin and enoxolone to curb CD38 activity, the study markedly increases the efficiency of NAD⁺ utilization. The findings offer both a novel target and a practical formulation strategy for next-generation anti-aging skincare products, combining strong scientific rationale with clear translational potential.

Reference

[1] Kang S, Park J, Cheng Z, et al. Novel Approach to Skin Anti-Aging: Boosting Pharmacological Effects of Exogenous Nicotinamide Adenine Dinucleotide (NAD⁺) by Synergistic Inhibition of CD38 Expression. Cells, 2024, 13(21): 1799.

*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.

by GSHWORLD

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