NAD+ has become increasingly relevant in aging research, primarily due to its well-documented decline with age. Human skin, in particular, shows a notable decrease in NAD+ levels, dropping approximately 50% across the adult lifespan1. This age-related reduction of NAD+ in the skin is now being recognized as a key factor contributing to visible signs of skin aging.
Here we discuss current research linking NAD+ to skin aging and explore practical strategies aimed at boosting NAD+ levels to potentially slow or reverse skin aging processes.
The role of NAD+ in skin cell function: energy, defense and inflammation
NAD+ is essential for fundamental skin cell functions, notably beginning with its critical role in cellular energy production. As a key substrate in mitochondrial respiration, NAD+ supports the efficient generation of ATP, vital for energy intensive processes such as collagen synthesis, cell turnover, and tissue repair.
However, aging is associated with declining NAD+ levels, partly driven by the increased activity of CD38, an NAD-consuming enzyme often linked to inflammation. This decline negatively impacts mitochondrial function, particularly through reduced activity of SIRT3, leading to cellular energy deficits and impaired skin function2. Preclinical studies suggest that restoring NAD+ levels can reduce mitochondrial dysfunction and promote mitophagy, preserving cellular health3. Beyond energy production, NAD+ plays a critical role in the skin’s defense against oxidative stress, a continuous challenge due to UV radiation exposure and metabolic byproducts. NAD+ acts as an essential cofactor for sirtuins such as SIRT1 and SIRT3, which regulate antioxidant defense and repair mechanisms necessary for neutralizing reactive oxygen species (ROS). Enhancing NAD+ levels in skin cells has demonstrated a reduction in oxidative stress markers and decreased mitochondrial ROS production, emphasizing NAD+’s protective role3. Additionally, NAD+ balance is closely connected to managing skin inflammation, or “inflammaging.” Adequate NAD+ levels enhance sirtuin-mediated suppression of inflammatory pathways (e.g., SIRT1 inhibition of NF-κB). However, chronic inflammation, possibly driven by cellular senescence, can accelerate NAD+ breakdown via enzymes like CD382, creating a detrimental feedback loop: inflammation reduces NAD+, and reduced NAD+ impairs inflammatory control. Preliminary evidence indicates that maintaining NAD+ levels may help reduce systemic inflammation4. Therefore, preserving NAD+ homeostasis is critical for maintaining integrated skin health through its roles in energy metabolism, oxidative defense, and inflammatory regulation.
NAD+ and DNA repair: protecting skin from UV-induced damage
A major contributor to skin aging is the buildup of DNA damage, primarily caused by exposure to UV radiation. Efficient DNA repair mechanisms are vital for preventing lasting damage, which can lead to signs of photoaging, such as wrinkles and pigmentary changes, and increase cancer risk. NAD+ plays a critical role as a substrate required by important DNA repair enzymes, including poly(ADP-ribose) polymerases (PARPs) and sirtuins like SIRT1 and SIRT6, which coordinate responses to DNA damage and facilitate repair processes4. As NAD+ levels decline with age, the capacity of these DNA repair systems is compromised, resulting in an increased accumulation of DNA damage and heightened cellular senescence. This relationship is supported by observations of aged skin exhibiting elevated DNA damage alongside reduced NAD+ and sirtuin activity4. Clinical evidence further illustrates the significance of NAD+ for skin health. A phase 3 randomized clinical trial demonstrated that oral supplementation with nicotinamide (a vitamin B3-derived NAD+ precursor) at a dosage of 500 mg twice daily improved DNA repair in UV-exposed skin. Remarkably, this intervention led to a significant 23% reduction in new cases of non-melanoma skin cancer over 12 months among high-risk individuals5. These findings highlight how maintaining sufficient NAD+ levels can enhance genomic stability and protect skin cells from environmental stressors, particularly UV radiation.
Strategies to support skin’s NAD+ levels
So, knowing how vital NAD+ is for youthful skin, what can you actively do to support its levels as you age? Current research suggests combining lifestyle approaches with targeted supplementation. Here’s what current evidence supports for maintaining NAD+ and promoting skin vitality:
1. Boosting NAD+ from within: diet and supplementation
- Vitamin B3: Research indicates that adequate dietary intake of Vitamin B3 (niacinamide or niacin) is crucial as it directly supports NAD+ synthesis in the body. Good dietary sources include poultry, fish, brown rice, and legumes.
- Polyphenols: Including plenty of colorful fruits and vegetables in the diet provides beneficial plant compounds called polyphenols (like quercetin). Preclinical evidence suggests these compounds might help preserve NAD+ by potentially inhibiting enzymes like CD38 that consume it3. Additionally, their anti-inflammatory properties indirectly support NAD+ balance.
- NAD+ supplements: NAD+ precursors like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN) are commercially available and have demonstrated effectiveness in raising NAD+ levels in humans. Ongoing research is exploring their specific impacts on skin health. A small clinical study involving middle-aged women found that supplementation with NR notably improved skin hydration, elasticity, and reduced wrinkles after several weeks6.
2. Getting active: Exercise for cellular health
Scientific studies demonstrate that physical activity is a natural and effective way to enhance NAD+ metabolism. Both endurance and resistance exercises have been shown to increase the activity of key enzymes like NAMPT, involved in the NAD+ salvage pathway, potentially raising NAD+ levels in various tissues. Exercise also activates protective cellular pathways, including those involving sirtuins and antioxidant defenses, contributing positively to overall cellular health and potentially benefiting skin vitality. Thus, consistently incorporating cardiovascular and strength training exercises into your routine can support cellular function and skin health.
3. Protecting your skin: Sun protection and skincare
- Make sunscreen non-negotiable: Protecting your skin from UV radiation is perhaps the most critical daily habit for preserving NAD+ levels. Excessive UV exposure causes significant DNA damage, which triggers repair processes that heavily consume NAD+. Regular application of broad-spectrum sunscreen helps limit UV-induced NAD+ depletion, allowing the skin’s NAD+ resources to remain available for essential maintenance and rejuvenation functions.
- Skincare with topical NAD+ boosters: Your skincare routine can also support NAD+ levels and skin health. Products containing antioxidants offer protective benefits. Specifically, topical niacinamide (Vitamin B3) stands out due to robust research demonstrating its effectiveness in reducing signs of aging, such as wrinkles, redness, and pigmentation. Niacinamide works partly by serving as an NAD+ precursor directly in the skin’s surface layers, enhancing its protective and restorative capacity7.
Author: Federico Bertoli
Sources:
1. McReynolds, M. R., Chellappa, K. & Baur, J. A. Age-related NAD+ decline. Exp. Gerontol. 134, 110888 (2020).
2. Camacho-Pereira, J. et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metab. 23, 1127–1139 (2016).
3. Kang, S. et al. Novel Approach to Skin Anti-Aging: Boosting Pharmacological Effects of Exogenous Nicotinamide Adenine Dinucleotide (NAD+) by Synergistic Inhibition of CD38 Expression. Cells 13, 1799 (2024).
4. Conlon, N. J. The Role of NAD+ in Regenerative Medicine. Plast. Reconstr. Surg. 150, 41S-48S (2022).
5. Chen, A. C. et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N. Engl. J. Med. 373, 1618–1626 (2015).
6. Zhang, H., Wang, L., Huang, J. & Zhao, L. Skin-Condition-Improving Effects of Nicotinamide Riboside Contained Supplement: A Randomized Clinical Trial in Naturally Aged Asian Women. Curr. Dev. Nutr. 8, 102227 (2024).
7. Camillo, L., Zavattaro, E. & Savoia, P. Nicotinamide: A Multifaceted Molecule in Skin Health and Beyond. Medicina (Mex.) 61, 254 (2025).
Leave a Reply