Scientists Can Reverse DNA Aging in Mice

Researchers have found a way to protect a mouse’s DNA from the damage that comes with aging, and they’re ready to test it in people.

Dr. David Sinclair, from Harvard Medical School, and his colleagues reveal their new findings in the latest issue of Science. They focused on an intriguing compound with anti-aging properties called NAD+, short for nicotinamide adenine dinucleotide. It’s been known that younger mice had more of it than older mice and back in 2013, the researchers found that when they boosted the NAD+ levels in older mice, they looked, biologically, like much younger animals.

In the latest paper, the scientists revealed new details on how NAD+ works to keep cells young. Sinclair put drops of NAD+ into the water of a group of mice, and within a couple of hours, their NAD+ levels started to rise. Within the first week, the scientists saw obvious age reversal in muscle and improvements in DNA repair. “We can’t tell the difference between the tissues from an old mouse that is two years old versus a young mouse that is three to four months old,” Sinclair says.

The reason they think NAD+ has these effects is because the compound is linked to DNA repair functions in the body. Each time cells divide, DNA copies itself—but it’s not always a perfect process, and errors are sometimes introduced, causing damage to the DNA. (Exposure to certain chemicals, environmental pollutants and medical radiation from CT scans can also damage DNA.) Normally, most of these insults can be repaired, as long as there’s enough of the a DNA-repair compound, called PARP1.

This repair compound and NAD+ are intimately linked. When NAD+ levels are high, PARP1 is activated and can do its job. But when NAD+ levels drop—as they do in older people—PARP1 also starts to decline, which leads to accumulating DNA damage.

Scientists have harnessed this to target cancer cells. A class of cancer drugs called PARP inhibitors, which are prescribed for breast cancer, interfere with PARP’s ability to repair DNA in the tumor, which ultimately leads to their demise. But not all people who take the drug respond well to it, and manipulating NAD+ levels may be one way to enhance their response.

The ultimate test, of course, will be to see if such quick reversal of aging in tissues is also possible in people. Sinclair co-founded a company in Boston, called MetroBiotech, to take the leap of developing and testing a human-grade version of NAD+. He has formulated a capsule version of a precursor to NAD+ called nicotinamide mononucleotide (NMN)—a naturally occurring compound found in small amounts in foods like broccoli, cucumber, avocado and edamame—and plans to test 25 people to see if the compound is safe.

If those studies are positive, Sinclair hopes the idea of using NAD+ to protect DNA from age-related damage might have broader applications, such as shielding cancer patients from the side effects of radiation treatments or even protecting people who are exposed to higher radiation work environments from DNA damage.

“The idea is to protect the body from radiation exposure here on earth, either naturally occurring or doctor-inflicted,” he says. “If I were going to have an X-ray or a CT scan, I would take NMN beforehand.” He already has plans to go even farther than earth: NASA is collaborating with Sinclair’s group on the human tests to see if it’s possible to insulate astronauts from the effects of cosmic radiation in space.