How NAD Keeps Your Cells Energized and Slows Down Aging
From The University of Bergen - January 27, 2025
Scientists have uncovered a key function of NAD, a molecule crucial for energy and cellular repair. Mitochondria act as NAD storage units, but if drained over time, they can accelerate aging and disease. Promising treatments focus on boosting NAD levels to combat these effects.
NAD, a vital molecule for cellular energy and DNA repair, plays a central role in aging and prevention of diseases like cancer and neurodegeneration.
Recent research reveals how mitochondria act as reservoirs for NAD, supporting cells during increased demand. This insight opens doors to therapeutic strategies for mitigating aging and related diseases.
NAD: The Molecule Essential to Life
At the core of this groundbreaking discovery is a molecule called NAD, short for Nicotinamide Adenine Dinucleotide.
Professor Mathias Ziegler from the Department of Biomedicine at the University of Bergen (UiB), who led the international research team behind the study, highlights its importance:
“The fascinating thing about NAD is that the molecule is essential to life, as it plays critical roles in all cellular processes. Therefore, dysregulated NAD levels are involved in aging processes as well as many pathologies ranging from cancer to diabetes and neurodegenerative diseases. And the reason for this is that it holds a key position in both energy metabolism and the regulation of vital functions,” he says.
How NAD Fuels Cellular Energy
All bodily functions rely on energy — without it, we can’t run, breathe, or even think. Our bodies, and more specifically our cells, get this essential energy from the food we eat. Nutrients like sugars and fats are broken down and converted into a form of energy that cells use to power everything they do.
“NAD is central to these conversions as it functions like a rechargeable battery. It is charged by the energy retrieved from food and passes it on to fuel all cellular activities. An important part of this energy transfer takes place in cellular structures called mitochondria, which are also referred to as the powerhouse of the cell,” Ziegler explains.
Aging, DNA Repair, and NAD Demand
Crucially, NAD also contributes to many other vital functions throughout the cell. It serves as a chemical signal to regulate key cellular events including gene expression and DNA repair, which take place in the cell nucleus.
“Interestingly, during aging, our DNA may accumulate damage which, in turn, will increase the demand for NAD molecules. Indeed, we see that cellular NAD levels decrease as we age, and it is assumed that increased DNA repair activity is one of the main reasons for this decline,” explains Ziegler.
“The problem arises when the mitochondria or their NAD store are affected or tapped over extended periods of time.”
But how do cells cope with the increased demand for NAD and do decreased NAD levels necessarily result in pathological conditions?
To answer these questions, Ziegler and his team developed models to study how cells react to reduced NAD levels as they occur during aging.
They had previously developed a method that enabled them to detect cellular NAD molecules and their distribution in living cells.
In addition, they now implemented advanced analytical techniques, including high-resolution mass spectrometry, to study the cellular dynamics of NAD-dependent processes.
As a result, the researchers discovered a hitherto unrecognized role of mitochondria in the maintenance of cellular NAD levels:
“These organelles serve as an NAD reservoir that is filled when cells function normally, and it supplies the cell with NAD when there is an increased demand,” explains Lena Høyland, PhD student and first author of the study.
Employing gene-technological methods such as CRISPR-Cas9 genome editing they were able to establish the molecular mechanisms of how mitochondria counteract cellular NAD decline.
“Decreased cellular NAD levels thus appear to be generally well tolerated by the cells,” she says.
“The problem, however, arises when the mitochondria or their NAD store are affected or tapped over extended periods of time. This can have fatal consequences since the cells may no longer have sufficient NAD “battery capacity” to drive vital, energy-dependent processes,” Professor Ziegler adds.
Exploring NAD Supplementation in Aging
Research over the past years has established that mitochondrial dysfunction and lowered cellular NAD levels represent characteristics of aging, and age-related disorders, such as dementia or neurodegenerative diseases.
Based on their new findings, the team of researchers believes that excessive depletion of mitochondrial NAD might constitute a key factor leading to dysfunctional cellular powerhouses and thus aging-associated diseases.
Indeed, initial clinical trials in Norway and internationally using therapeutic supplementation approaches aiming to increase NAD levels have provided encouraging results.
“We are very excited about having discovered yet another mechanism potentially involved in disease development and progression,” says Høyland, and Ziegler concludes:
“Our study also demonstrates the importance of basic research to identify promising targets to slow aging and to treat aging-related diseases.”
The results have been published in the renowned journal Nature Metabolism and featured in a News and Views article in the same issue.
Reference: DOI: 10.1038/s42255-024-01174-w
How to increase NAD+
Perhaps the best way to supplement declining NAD+ is through NAD+ ezPen Injection Therapy. Unlike supplementing your NAD+ via IV Drip, which delivers a huge dose all at once, the NAD+ ezPen Injection doses a little NAD+, painlessly, a few times per week, enhancing then maintaining your daily NAD+ levels. Good NAD+ levels in your body will help your body run optimally and, with over 500 biological pathways using NAD+, you will see how important NAD+ really is. NAD+ ezPen Injections help to ensure that it’s absorbed by the bloodstream, rather than being broken down in the digestive system, thereby delivering maximum benefits to your body. You get the benefits of NAD more quickly than you might with other delivery systems, such as the oral route, so you experience a faster, more effective treatment outcome.
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