The Science of NAD+: What Peer-Reviewed Research Actually Says About Your Skin

What NAD+ Is and Why Science Cares So Much About It

NAD+ is a coenzyme — a helper molecule — present in every living cell. Its primary role is to accept and donate electrons in metabolic reactions, which is what allows your cells to convert food into usable energy. But that is only the beginning of what it does.

NAD+ also serves as a substrate — a fuel source — for two families of enzymes that are central to aging biology: the PARP enzymes (poly ADP-ribose polymerases), which repair damaged DNA, and the sirtuins, a family of proteins that regulate inflammation, stress response, gene expression, and cellular repair. Both families require NAD+ to function. When NAD+ levels fall, both systems underperform simultaneously.

This is not a niche finding. A landmark 2021 review published in Nature Reviews Molecular Cell Biology by Covarrubias and colleagues described NAD+ metabolism as one of the most critical regulatory systems in the biology of aging — influencing cellular energy, genome integrity, inflammation, and longevity across multiple organ systems, including skin. The reason longevity researchers, pharmaceutical companies, and dermatologists are all paying attention to the same molecule is that NAD+ sits at the intersection of virtually every process that defines how we age.

The Decline Is Real, Documented, and Measurable in Human Skin

The most important fact to understand about NAD+ and aging skin is that its decline is not theoretical. It has been measured directly in human skin tissue, across decades of life, using tissue samples from real patients.

A study published in PLOS ONE by Massudi and colleagues examined skin samples from consenting patients aged between newborns and 77 years old. The researchers found that NAD+ levels declined significantly with age in human pelvic skin. Alongside falling NAD+ levels, they documented a corresponding rise in markers of oxidative stress and greater PARP activity — indicating that the DNA repair system was consuming more NAD+ in aging skin precisely because there was more damage to repair. The system was working harder with a smaller fuel supply.

This finding matters because it establishes a clear mechanism. It is not simply that older skin makes less collagen. It is that older skin has less cellular energy to run the repair systems that maintain collagen production, protect DNA from daily damage, and regulate the inflammatory processes that accelerate visible aging. Research has consistently shown that NAD+ levels fall by approximately 50 percent between young adulthood and middle age. For women, some evidence suggests the decline may be further compounded by hormonal shifts, making the NAD+ conversation particularly relevant to skin health after 35.

What Happens in Your Skin Cells When NAD+ Drops

Understanding the downstream consequences of NAD+ decline requires looking at what the two NAD+-dependent enzyme families actually do in skin.

The PARP enzymes — particularly PARP-1 — function as the DNA damage response team. Every day, UV radiation, pollution, and normal metabolic processes create breaks and lesions in the DNA of your skin cells. PARP-1 detects these breaks and initiates repair by consuming NAD+ to attach repair-signaling molecules to damaged proteins. Under conditions of moderate damage, this works efficiently. But as NAD+ levels decline with age, the response becomes compromised. Unrepaired DNA damage accumulates. Cells either age prematurely (a process called senescence) or die, and the skin's capacity for self-renewal slows.

The sirtuin family tells a parallel story. Sirtuins, especially SIRT1 and SIRT6, require NAD+ to perform their regulatory functions in skin cells. A review published in Trends in Cell Biology by Imai and Guarente documented how sirtuin activity declines in parallel with NAD+ — and how this directly affects aging biology. In dermal fibroblasts specifically, research has shown that silencing SIRT6 disrupts collagen metabolism — reducing collagen production and increasing the activity of the enzymes that break it down. In plain terms: without adequate NAD+ to power SIRT6, your skin makes less collagen and loses more of it.

A 2024 study published in Cells by Kang and colleagues investigated the direct pharmacological effects of exogenous NAD+ on human skin fibroblasts. The researchers found that NAD+ exerted protective effects against both UV-induced aging and intrinsic chronological aging in skin cells, and that these effects were mediated through improved sirtuin activation, enhanced autophagy, and better mitochondrial function. Critically, they were working with the kind of cells found in human dermis — making the findings directly relevant to skin aging.

The Evidence for NMN and NR as Topical and Oral Precursors

Because NAD+ itself is relatively large and unstable as a topical ingredient, a significant body of research has focused on its precursors — NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside). Both are converted by the body into NAD+ through the salvage pathway and have been shown to meaningfully raise NAD+ levels.

On the topical side, a 2025 study published in the Journal of Cosmetic Dermatology by Betsuno and colleagues examined whether NMN could actually penetrate the skin barrier when formulated in a cosmetic base. Using artificial skin membranes designed to replicate human skin, the researchers confirmed that NMN did penetrate and was detectable in the papillary dermis — the upper layer of the dermis where fibroblasts live and collagen is produced. The same study confirmed that NMN increased Collagen Type 1 production in human fibroblasts treated with the compound.

This is significant because it addresses the most common skepticism about NAD+ in skincare: does it actually get where it needs to go? This study provides direct evidence that NMN, at least in an appropriate cosmetic formulation, can reach the dermal layer and stimulate collagen production once it arrives.

On the oral and systemic side, the evidence is more extensive. A 2025 review in Nature Aging by Zhang and colleagues described the growing body of clinical work on NAD+ precursors in humans, noting both the therapeutic promise and the importance of formulation and delivery in determining outcomes. Separately, a landmark clinical trial conducted at Chiba University using NR supplementation in patients with Werner syndrome — a genetic disorder of accelerated aging — found that boosting NAD+ levels reduced skin ulcers, improved cardiovascular markers, and appeared to slow tissue breakdown. This was the first human clinical trial to show that NAD+ replenishment could protect skin tissue in a clinically measurable way.

What the Research Says About NMN Specifically in Skin Cells & CD38 Problem

A 2025 study published in a peer-reviewed journal examined the gene expression profiles of skin fibroblasts exposed to NMN. The findings provided what the researchers described as essential mechanistic evidence for the anti-aging effects of NMN in skin cells — covering multiple biological pathways including energy metabolism, oxidative stress response, and cellular repair.

Separately, a 2024 in vitro study using human fibroblasts demonstrated that NAD+ protected skin cells from both extrinsic aging driven by UV light and intrinsic chronological aging. The protective mechanism worked through three parallel pathways: improved sirtuin activation, stimulated autophagy (the cellular self-cleaning process), and enhanced mitochondrial function. Each of these is a recognized hallmark of skin aging when it underperforms.

The collagen connection runs through multiple studies. Research consistently shows that fibroblasts with higher NAD+ levels produce more collagen and are better protected from the enzymes that degrade it. The papillary dermis findings from the 2025 topical NMN permeation study are particularly relevant here — because the papillary dermis is precisely where fibroblasts reside and where collagen is synthesized.

What the body of evidence collectively describes is a cascade: NAD+ declines with age, PARP and sirtuin activity falls, DNA repair slows, collagen production drops, inflammation rises, and skin visibly ages faster than it would if the cellular fuel supply were maintained.

The CD38 Problem: Why Your Body Actively Depletes Its Own NAD+

One of the more striking findings in recent NAD+ research is that the decline is not entirely passive. The body does not simply stop making NAD+ as it ages — it also begins actively destroying it at a faster rate.

The culprit is an enzyme called CD38. CD38 is an NAD+-consuming enzyme found on the surface of immune cells. Research published by Chini and colleagues in 2020 showed that CD38 expression increases with age and is further driven upward by chronic low-level inflammation — the same kind of persistent background inflammation that accelerates aging in skin and other tissues.

As CD38 activity rises, it consumes NAD+ reserves faster than aging cells can replenish them. This creates a compounding deficit: slower synthesis on one side, faster consumption on the other.

The 2024 study by Kang and colleagues addressed this directly, demonstrating that combining exogenous NAD+ with inhibitors of CD38 expression — specifically plant compounds quercetin and enoxolone — produced significantly greater anti-aging effects in human fibroblasts than NAD+ alone. The synergistic approach amplified NAD+'s protective effects against UV-induced aging and intrinsic aging by improving both availability and utilization of the molecule.

This research has practical implications for how NAD+ skincare products should be formulated. An ingredient list that addresses the CD38 consumption problem — or that pairs NAD+ precursors with polyphenols known to support NAD+ retention — is operating at a more sophisticated level than products that simply add NAD+ to a formula and hope for the best.

How to Read This Research Honestly

The evidence that NAD+ declines in human skin with age is solid. The evidence that this decline is mechanistically connected to impaired DNA repair, reduced collagen production, and accelerated cellular aging is well-supported across multiple independent research groups. The evidence that NMN can penetrate skin tissue and stimulate collagen in fibroblasts is newly published but rigorous. The evidence that oral NAD+ precursors safely raise NAD+ levels in humans is consistent across multiple human trials.

What remains less established is the dose-response relationship for topical formulations — how much NMN or NAD+ in a cream translates to how much measurable improvement, over what timeframe, and across different skin types and ages. The clinical trial data on topical products specifically is still building. This is the honest position of a pharmacist who formulates based on the science that exists, not the science we hope will exist.

The peer-reviewed literature on NAD+ and skin aging supports the following conclusions:

NAD+ levels decline measurably in human skin with age, and this decline is directly connected to reduced DNA repair capacity, impaired collagen production, and accelerated aging biology. This is not marketing language. It is the finding of independent researchers working with human tissue samples. NMN penetrates skin tissue when properly formulated and increases collagen production in dermal fibroblasts — confirmed in a 2025 Journal of Cosmetic Dermatology study using skin-mimicking membranes. Sirtuin activity in skin cells — particularly SIRT1 and SIRT6 — is directly dependent on NAD+ availability and directly regulates how much collagen is made versus broken down. Oral NAD+ precursors safely raise NAD+ levels in humans and have been shown to protect skin tissue in clinical settings. CD38 is an active driver of NAD+ depletion and addressing it alongside NAD+ supplementation produces greater outcomes. The most effective strategy is comprehensive: topical formulations that deliver NAD+ precursors to the dermis, paired with internal support that addresses the systemic decline that topical products alone cannot fully reverse.

This is what the science says. It is also why, at B NOOR, we formulate the way we do — starting from the mechanism, building toward the outcome, and holding every product to the standard of the research behind it.