A form of vitamin B3 taken as a supplement may reverse muscle frailty associated with aging by boosting levels of NAD, a molecule that helps generate energy from food nutrients, researchers report. The findings may lead to new ways of ameliorating certain aspects of muscle dystrophy.
The recent study, “Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle,” was authored by David Frederick, PhD, from the Perelmann School of Medicine at the University of Pennsylvania, and colleagues, and published in the journal Cell Metabolism.
Mitochondria are the part of the cell responsible for the generation of energy to power body functions. In mitochondria of multiple tissues, several enzymes work together to make fresh NAD, which is necessary to provide support for the process of energy generation from fats and sugars from ingested food. However, as people age, NAD levels start declining in the mitochondria, and less energy is produced to fuel such efforts as muscle function.
To understand exactly what would be the effect of low levels of NAD in muscle cells, the researchers attempted to simulate this normal aspect of the aging process by generating mice with restricted amounts of NAD in their muscle tissue. They observed that young mice with an 85% reduction in muscular NAD levels were still able to maintain spontaneous activity or treadmill endurance. As mice became adults, however, their muscles progressively weakened and their muscle fibers atrophied, similar to what occurs in a muscular disease.
“Their muscle tissue looked like that of Duchenne’s muscular dystrophy [DMD] patients,” Joseph Baur, PhD, and the study’s lead author, said in a news release. “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.”
The team then investigated the effects of increased levels of NAD in muscle function. To do so, they induced the expression of the Nampt enzyme, which participates in the formation of fresh NAD. As expected, the induction of Nampt prevented the natural decay of NAD, and preserved part of the exercise capacity in older animals.
Researchers also observed that feeding mice with a form of vitamin B3, called nicotinamide riboside (NR), which is a NAD precursor, also reduced muscle weakening in older mice. Although supplements to counteract the natural decay of NAD levels associated with aging are available on the market, no study had addressed the association between reduced NAD levels and muscle function.
“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,” Frederick said in the release. “It appears that a relatively small enhancement in muscle NAD can have profound functional consequences in this setting.”
Together, the findings showed that strategies to induce the production of NAD may be suitable to reversing NAD decline and muscle weakening in aging adults. They also raise the question as to whether certain muscular diseases may have an underlying decay in NAD levels as well, and, if so, whether restoring NAD levels would ameliorate some symptoms of these diseases.