Despite an 85% reduction in NAD+ levels, mice maintained normal muscle health and function, according to new research from the Treebak Group. Since natural aging typically causes only up to a 30% decline in NAD levels, these findings cast doubt on the purported health benefits promoted by NAD+ supplement companies.
In the Netflix documentary Don’t Die: The Man Who Wants to Live Forever, biotech entrepreneur Bryan Johnson reveals he takes over 50 supplements a day as part of his quest to reverse aging. Among them are NAD precursors, compounds meant to boost levels of a molecule called NAD+, which plays a key role in cellular energy and other essential processes. Since NAD+ levels decline significantly with age, particularly in skeletal muscle, many believe supplementing could help preserve health and slow the aging process.
But new research suggests that this popular biohack may not deliver the promised benefits.
A study from the Treebak Group at the University of Copenhagen’s NNF Center for Basic Metabolic Research, published in Cell Metabolism, tested what happens when NAD+ levels in skeletal muscle are severely reduced. In mice, researchers knocked NAD+ levels down by 85%, yet saw no signs of accelerated aging or disruptions to whole-body metabolism.
“Our results suggest that skeletal muscle can tolerate substantial NAD depletion without loss of function or accelerated aging,” says Associate Professor Jonas Treebak, corresponding author of the study that was published in Cell Metabolism. “This challenges the prevailing view that NAD+ decline is a primary driver of muscle aging and frailty.”
NAD helps mitochondria in cells produce energy in the form of ATP. However, scientists do not fully understand the extent to which the decline in NAD affects mitochondrial function and aging in general. For example, how low can NAD levels drop before an effect can be noticed?
Healthy skeletal muscle function not reliant on high NAD levels
To study these questions, the scientists created a special type of mouse whose NAD levels could be reduced specifically in skeletal muscle after they became adults. This allowed the scientists to test the effect on mature muscle, avoiding any confusion with how NAD might affect muscle as it develops.
Even though these mice had much lower NAD in their muscles, their muscle size, overall health, strength, and exercise performance were all normal. Detailed studies of the cell’s genes, proteins, mitochondria, and DNA markers, called DNA methylation, remained normal despite the low NAD levels.
While the mice with low muscle NAD did show increased energetic stress during exercise and some minor changes in how they processed energy, the overall markers of their whole-body and muscle health stayed the same as regular mice, even after they lived their entire lives with low muscle NAD.
“Contrary to what might have been expected, healthy skeletal muscle function is not as reliant on high levels of NAD as previously thought. Importantly, our findings indicate that reducing muscle NAD levels well beyond the modest drops seen with normal aging does not cause muscle weakness or make the muscle age faster,” says Sabina Chubanava, who carried out the research as a PhD student and Postdoc in the Treebak Group.
Reference: “NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging” by Sabina Chubanava, Iuliia Karavaeva, Amy M. Ehrlich, Roger M. Justicia, Astrid L. Basse, Ivan Kulik, Emilie Dalbram, Danial Ahwazi, Samuel R. Heaselgrave, Kajetan Trošt, Ben Stocks, Ondřej Hodek, Raissa N. Rodrigues, Jesper F. Havelund, Farina L. Schlabs, Steen Larsen, Caio Y. Yonamine, Carlos Henriquez-Olguín, Daniela Giustarini, Ranieri Rossi and Jonas T. Treebak, 30 April 2025, Cell Metabolism.
DOI: 10.1016/j.cmet.2025.04.002
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7 Comments
Another snake oils salesman.
We got one in DC, why would I pay exorbitant prices for something that provides false hope.
After all.
Who wants to live forever?
You are prematurely drawing conclusions on a study that you have not even read. There are actually studies show NMN improves health and slows aging.
It isn’t ‘popular’. I take a variety of supplements; it’s not something that stands out in my memory on the shelves of health food and supplement stores. It doesn’t even have an entry in Nutrition Business Journal’s ranking of top 100 supplements.
The label would be “trending”.
A fool and their money are soon parted.
A lot of people read these things but the perpetrators seem intent on keeping it all within their small circle. Having read the whole article (I am a qualified science teacher) I still don’t know WTF the NAD acronym stands for.
NAD stands for Nicotinamide Adenine Dinucleotide.
Muscle wastage and metabolic disorders are caused by dysregulated estrogen receptors, not NAD levels. NAD has only a minimal impact on muscle.
What NAD does is involved in entirely different metabolic pathways involved in stabilization of the electron transport chain involved in obesity and liver issues.
One could argue its linked to NOX4 expression that drives beneficial inflammation involved in muscle growth, being downstream from NAD. Even that is a stretch.
This study seems to a unique form of gas lighting.