Approximately ten thousand times each day, the DNA in our cells receives some damage, but most of that damage is repaired by our cells' built-in DNA repair systems. The efficiency of these DNA repair systems decline with age, however, and that's thought to lead to age-related health problems and cancer.

A recent paper published in Science shows that a chemical used in the DNA repair process, nicotinamide adenine dinucleotide (NAD+), has a concentration that declines with age. This decline may drive the age-associated accumulation of DNA damage—a finding that suggests supplementing NAD+ might offset some of the effects of aging.

The team behind the paper used human embryonic kidney cells (which grow well in the lab) to look at the role of this chemical. The authors found that NAD+ binds to the protein “deleted in breast cancer 1” (DBC1), which—as its name implies—was previously implicated in cancer. DBC1 normally binds to and inhibits another protein that performs DNA repair. But NAD+ blocks this interaction, releasing the inhibition on DNA repair.

Therefore, as NAD+ concentrations decline with age, it's possible there is insufficient NAD+ to bind to the DBC1 protein, leaving it free to block DNA repair.

To test this proposed mechanism in a living organism, the authors used aging mice. As expected, NAD+ concentrations declined as the mice aged. With its decline, DBC1 was increasingly binding to and shutting down the DNA repair enzyme. The authors then gave the mice the chemical precursor to NAD+, which should restore their NAD+ concentrations. Once the mice were given this treatment, their DNA repair activity increased, and the levels of DNA damage were reduced.

It's important to note that this is in comparison with untreated, aged mice. The effect was not quantified relative to the DNA repair in young mice, so we don't know how much of a restoration this is.

This paper does not definitively explain all age-related increases in DNA damage—there may be other mechanisms at play. But it does suggest there's an NAD+ dependent mechanism that may contribute to this phenomenon. Based on this finding, the authors suggest that replenishing NAD+ concentrations could alleviate the effects of certain DNA-damaging exposures, such as chemotherapy and radiation.

While the data looks compelling, more research is needed on the potential consequences of elevating NAD+ levels before this technique is employed in humans; this study was small and contained only three to five mice for each of the various experiments. We still don’t know why NAD+ concentration declines with age, and we don’t know what other cellular functions might be controlled by this decline in NAD+ availability.

Once the effects of NAD+ are more fully characterized, this compound could be an exciting new way to limit DNA damage. Increasing NAD+ concentration could also provide more quality years of life.

Science, 2017. DOI: 10.1126/science.aad8242 (About DOIs)