Muscle Function Holds Up Even With 85% Less NAD+, Casting Doubt on the Ageing-Culprit Hypothesis
Mice in which NAD+ synthesis in skeletal muscle was blocked, cutting it by 85%, kept normal muscle function and whole-body metabolism throughout life.
A study published in Cell Metabolism suggests that the decline in NAD+ (nicotinamide adenine dinucleotide), often cited as a key cause of ageing, may not be directly linked to the decline in skeletal muscle function. It was led by researchers at the University of Copenhagen in Denmark.
Removing the NAD+ synthesis enzyme in adult muscle
NAD is a molecule that serves as an electron carrier in energy metabolism and is used to modify many regulatory proteins, and its decline with age has been linked to ageing. The researchers removed NAMPT (nicotinamide phosphoribosyltransferase), a key enzyme in NAD+ synthesis, only in the skeletal muscle of adult mice, creating a model in which the amount of NAD+ in muscle fell by 85%.
Even so, muscle structure, contractile force and exercise endurance were maintained. Mitochondrial respiration was not impaired, and there were no clear changes in the muscle transcriptome or proteome profiles. Mice that lived their whole lives with low NAD showed no faster muscle ageing, and whole-body metabolism was also normal.
The researchers interpreted the results to mean that a decline in NAD may not be the cause of the age-related loss of muscle function. However, the results are limited to mouse skeletal muscle and cannot be applied directly to other organs or to people. The study also did not directly evaluate the effect of interventions that raise NAD.
- The NAD+ synthesis enzyme NAMPT was removed from the skeletal muscle of adult mice, lowering muscle NAD+ by 85%
- Muscle structure, contractile force, exercise endurance and mitochondrial respiration were all maintained
- Lifelong low NAD did not accelerate muscle ageing or cause whole-body metabolic problems
Limitations The results are limited to mouse skeletal muscle and do not directly show what a decline in NAD means in other organs or in people.
Original research
- Chubanava S, et al. · University of Copenhagen. NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging. Cell Metabolism. DOI: 10.1016/j.cmet.2025.04.002
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