Why NAD+ Matters—Far Deeper Than Anti-Aging Claims
NAD+ is an essential coenzyme found in every living cell that is required by mitochondria in energy production.
The following article is an opinion piece written by Mo Li. The views and opinions expressed in this article are those of the author and do not necessarily reflect the official position of Technology Networks.
We've all been there: researching vitamins or supplements that boost our energy, slow down aging, or provide other health benefits—often prompted by social media trends. However, without truly understanding the root causes of the issue we might be trying to address, we can overlook the factors that actually explain our health. We can end up treating symptoms we cannot name, with solutions built on science we haven't fully understood.
Over the past couple of years, longevity has become the defining buzzword of the health and wellbeing industry—reaching further into mainstream culture than ever before. As a stem cell biologist, my role and research interest intersect with this mainstream coverage.
Central to this discussion is NAD+: an essential coenzyme found in every living cell that is required by mitochondria to convert the nutrients from the food we eat into a usable form of fuel called adenosine triphosphate (ATP). Without enough NAD+, the mitochondria cannot efficiently convert nutrients into cellular energy.
What does this mean in practice? And how is this connected to longevity? Beyond energy production, NAD+ fuels the enzymes responsible for DNA repair and mitochondrial maintenance—the very processes that keep cells functioning as we age. As NAD+ levels fall, so does the cell's ability to repair itself, maintain its energy systems, and resist stress. Critically, NAD+ levels naturally decline with age—hence its recent relevance in the anti-aging conversation. It should be noted that this is perfectly natural as we get older.
What this anti-aging discussion often misses is a more important, underlying question: what is causing NAD+ to decline in the first place?
Research conducted by my team and I at King Abdullah University of Science and Technology (KAUST), published in the journal Communications Biology, found that the answer to this is more specific and more relevant to wider healthcare than aging alone.
We observed how human cells respond to acidic stress, using a precisely controlled bioreactor system. Our work found that even mild acidity can significantly disrupt cellular energy production, impair mitochondrial function, and trigger stress responses.
Acidic stress and why it matters?
To understand our findings, it is important to define the issue we were initially intending to explore: acidic stress.
Acidic stress is a condition in which cells are exposed to a low pH environment. It commonly occurs in inflamed tissues, aging organs, and tumors. This acidity disrupts cellular function and metabolism, potentially further acidifying the local cellular environment.
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Having said this, the reason acidic stress is so disruptive is that cells require strict pH levels to function properly. Healthy cells require constant and efficient energy production. When that balance shifts, the consequences move quickly through the entire cellular system.
Decoding the molecular blueprint
With this in mind, my team and I developed a multiomics framework examining three molecular datasets simultaneously. Using a purpose-built bioreactor system that stably maintains the cellular environment in a physiologically relevant manner, we isolated the effects of pH from other variables, replicated the mildly acidic conditions found in real human disease states, and observed what happened to human cells within them. Together, these datasets showed how acidity triggers NAD+ depletion, impairs mitochondrial function, activates immune stress responses, and causes mitochondrial genome instability.
- Metabolomics revealed that acidic stress directly depletes NAD+ and disrupts the cell's energy production, forcing cells into a far less efficient metabolic state.
- Transcriptomics showed how gene activity reorganizes under acidic conditions, activating immune pathways and escalating cellular stress responses.
- Epigenomics uncovered changes in how genes are regulated under acidic conditions, also revealing instability within the mitochondrial genome itself.
The mechanism behind the metabolomics finding is specific. Acidity activates an enzyme called PARP1, which rapidly consumes NAD+ as part of the cell's own stress response. At the same time, mitochondria are forced into a backup mode, and cells rely more heavily on glycolysis (splitting glucose for energy), a less efficient way to generate ATP. This metabolic shift can increase lactate production, which further acidifies the environment. The stress accelerates itself. Together, these three datasets do not describe separate problems. They describe one cascade: acidity triggers a NAD+ drain, energy production fails, the immune alarm activates, and the mitochondrial genome destabilizes. Each step follows the last. Surprisingly, supplementation with the NAD⁺ precursor nicotinamide mononucleotide, a molecule widely studied for its potential longevity-promoting effects, restored intracellular NAD⁺ levels and markedly increased cellular resilience to acidic stress.
Looking ahead
I believe this research has broader significance than a single study on pH. If acidity is actively driving NAD+ depletion as our research describes, then the implications reach into how we understand the progression of some of the most prevalent and complex health conditions we face today.
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A parallel can be drawn between NAD+ and collagen. Few wellness trends have travelled further or faster, and the science behind it is real. But the question the industry rarely stops to ask is: why is it breaking down? The answer lies in understanding the environment that destroys it.
The conversation around NAD+ has followed the same pattern. It has always been there, working inside every cell. What has changed is our understanding of what destroys it.
At KAUST, we strive to decode the molecular blueprint of human regeneration through stem cell science and bioengineering. Our research spans genome editing, single-cell mitochondrial DNA sequencing, and the development of stem cell-based human disease models.
Working within KAUST's BioMedical Sciences Division and Center of Excellence for Smart Health, across a platform that brings together genomics, bioengineering, and functional biology, the environment is built for precisely this kind of cross-disciplinary inquiry into cellular resilience. It is what makes research like this possible: not a single lens, but many.
My passion is to bring stem cell-based therapies to people and to translate the molecular precision of laboratory science into tools that genuinely improve lives. This research is a step in that direction.
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