Scientists at the University of Pennsylvania’s Perelman School of Medicine discovered that depletion of the mitochondrial factor NAD (nicotinamide adenine di-nucleotide) which helps maintain muscle function and endurance, ramps up muscle breakdown as mice age — a development that can be reversed by giving mice over-the-counter NAD-increasing supplements.
Researchers now suggest that the finding could potentially lead to treatment for multiple dystrophy.
Published in the journal Cell Metabolism, the study “Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle,” also showed that while increased levels of the mitochondrial factor throughout life did not benefit young mice, they did prevent normal muscle breakdown linked to aging.
Supplements that increase NAD in the body are available over the counter, and some athletes use them to prevent the decline in mitochondrial function leading to weaker muscles as they age. But the supplements are not required to go through rigorous testing required for prescribed medicines, so scientist are unsure if they can protect the muscles from aging.
The research team continued looking into the effects of NAD in mice, but focused on aging. They blocked a recycling pathway for making new NAD from old building blocks in skeletal muscles of mice, and discovered that young mice did not react with loss of muscle activity or endurance when levels of the factor were 85 percent lower than normal.
But in early adulthood, the changes caught up and muscles began breaking down. Researchers discovered that the muscles of NAD-depleted mice looked surprisingly like those seen in a disease.
“Their muscle tissue looked like that of Duchenne muscular dystrophy (DMD) patients,” Baur said. “The genes that were turned on and the presence of inflammatory immune cells in the muscles lacking NAD looked very similar to what we see in DMD.”
Researchers then started feeding mice with a factor turning into NAD in the body, a form of vitamin B3 called nicotinamide riboside (NR) obtained from the natural products company ChromaDex, which collaborated in the study.
The treatment completely reversed the muscle decline, and could activate mitochondria that had gone into a passive stage.
“At first, we were surprised by how rapidly NR was able to reactivate dormant mitochondria in muscle, despite being largely consumed by other cell types,” said David Frederick, PhD, a postdoctoral fellow in Baur’s lab. “It appears that a relatively small enhancement in muscle NAD can have profound functional consequences in this setting.”
An earlier study by the Perelman research team showed that dietary supplements did not seem to improve muscle performance in young mice.
“Finding out whether strategies to enhance the production of NAD will have any impact on muscle function in healthy individuals is a subject of much speculation,” Joseph Baur, PhD, an assistant professor of physiology at Perelman, said in a news release. “However, answering this question will have to wait for controlled clinical trials.”
Researchers are now following up on the Duchenne connection to see if NAD is depleted in some forms of muscular dystrophy, and if oral supplements could help lessen symptoms.
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