It is hardly a revelation to say that muscle function can decline with age, but some research into NAD, a helper molecule found throughout the body, suggests there may be ways to produce anti-aging effects capable of preserving or restoring muscle over time. The findings come courtesy of researchers at the University of Pennsylvania and also come with unexpected implications for patients with muscular dystrophy.
In Brief: NAD
NAD is a molecule found in most cells and is involved in a number of chemical reactions related to metabolizing fats and carbohydrates. NAD is especially important within the mitochondria, the power source of a cell. The body’s concentrations of NAD decline over time as part of the normal tissue aging process. The researchers wanted to look at the effects of NAD deficiency on the body.
NAD: The Study
The researchers examined mice in which they had disrupted the NAD salvage pathway—the enzyme chain that recycles the components of NAD to make new molecules. Specifically, the pathway was disrupted in the skeletal muscles in order to simulate the effects of aging. Interestingly, the mice could tolerate up to an 85% drop in NAD levels without showing declines in treadmill endurance or spontaneous ability.
However, once these mice reached adulthood (3-7 months old), they started showing progressive weakness and muscle atrophy. When inspected, the inflammatory immune cells and genes in the muscles looked very similar to those found in patients with Duchene’s muscular dystrophy (DMD). This is a genetic condition that leads to muscle degeneration and eventually death.
The next step in the research, after establishing that disruption to NAD levels could lead to muscle decline, was to see if a dietary approach could help improve the mice’s condition. The researchers fed the mice a form of vitamin B3, one of the NAD precursor components, and found that the muscular decline was completely reversed. In a separate test, it was found that inducing an overexpression of the Nampt enzyme (related to making NAD) would slow or prevent the natural decline of NAD levels from aging and preserve the mice’s exercise capability.
What This Means
Considering that inducing a NAD decline caused muscular effects similar to DMD, it seems possible that the researchers may have overshot the mark when trying to simulate the effects of aging. The similarity to muscular dystrophy has given the researchers plans to see if NAD deficiencies occur in normal DMD cases and, if so, whether supplementation might help.
The findings from the Nampt enzyme tinkering suggests that preventing the loss of NAD in the muscles helps produce some anti-aging effects and preserves a level of exercise capacity. This may suggest a way to combat age-related frailty, though the researchers point out that they don’t know how safe such an approach would be in the long term.
Since these tests were done on mice, the next stage would be seeing if the NAD findings can translate to observations of human muscle function in order to help determine possible clinical applications. For an already important helper molecule, it seems NAD might have further uses still left to discover.
Frederick, D., et al., “Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle,” Cell Metabolism, 2016; http://dx.doi.org/10.1016/j.cmet.2016.07.005.