Tuesday, August 23, 2016

The cover article of the August 2016 issue of Cell Metabolism describes the role of nicotinamide adenine dinucleotide (NAD) in maintaining muscle mass during aging and a potential benefit for supplementation with the NAD precursor nicotinamide riboside in muscle maintenance. NAD, which declines with aging is a compound made in the body that supports the mitochondria which serve as the cells' power plants.

Joseph Baur, PhD, of the University of Pennsylvania and colleagues generated mice in which the amount of NAD in specific tissues could be restricted in order to mimic normal aging. While these genetically modified mice tolerated an 85% decline in intramuscular NAD without a loss of spontaneous activity or exercise endurance, they began to experience weakness and muscle fiber atrophy in early adulthood. "Their muscle tissue looked like that of Duchene's muscular dystrophy [DMD] patients," reported Dr Baur, who is an assistant professor of Physiology at the University of Pennsylvania's Perelman School of Medicine. "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."

Giving the animals nicotinamide riboside, a form of vitamin B3 that acts as a precursor to NAD, resulted in complete reversal of muscle decline. "At first we were surprised by how rapidly nicotinamide riboside was able to reactivate dormant mitochondria in muscle, despite being largely consumed by other cell types," commented lead author David W. Frederick, PhD, who is a postdoctoral fellow in Dr Baur's laboratory. "It appears that a relatively small enhancement in muscle NAD can have profound functional consequences in this setting."

It was also discovered that overexpression of an enzyme known as Nampt that is involved in making NAD prevented NAD from declining over the life of the animal and helped preserve exercise capacity. "This was supporting evidence that strategies to enhance muscle NAD synthesis might help to combat age-associated frailty," Dr Frederick remarked.

Dr Baur plans to investigate whether restoring NAD could improve specific aspects of muscular dystrophy.