Cause of Aging in Mice Discovered and Reversed
Written by Madelyn Huttner, April 1, 2017
There are many internal and external ways our DNA gets damaged. Some examples include spontaneous conversions, replications errors, exposure to free radicals, etc. This damage contributes to aging and puts us at high risk for developing various cancers. DNA repair is the most important factor for cell survival and cancer prevention. But unfortunately, as we age our cells become less efficient at correcting DNA damage. Currently, scientists don’t understand why DNA repair declines with age.
But we have exciting news! A recent scientific discovery reveals a promising solution to this critical issue with aging. Scientists at Harvard Medical School have found a way to reverse the accumulation of DNA damage. An article in the latest issue of Science explains how NAD+ regulates protein-protein interactions involved in DNA repair.
“We recently showed that raising NAD levels in mice can reverse aspects of aging within just one week of treatment.” said David Sinclair, Ph.D., professor of genetics at Harvard University.
The Key Players
Nicotinamide Adenine Dinucleotide (NAD+) – coenzyme found in all cells associated with cellular regeneration and energy production
Poly (ADP-ribose) Polymerase (PARP1) – critical enzyme for DNA repair
Deleted Breast Cancer 1 (DBC1) – abundant protein known to regulate the initiate of tumor growth
Nicotinamide Mononucleotide (NMN) – precursor of NAD+
This study examined how PARP1 is inhibited by DBC1 by locking together. When NAD+ levels are optimal, NAD+ is able to bind to DBC1 and prevent the PARP1-DBC1 partnership. This study found replenishing the cells with NAD+ through NMN supplementation releases PARP1, so it is able to repair DNA.
The scientists at Harvard Medical School performed experiments by putting drops of NMN into the water consumed by mice for one week. NMN is required for the synthesis of NAD+and is thought to be more effective than it’s sister molecule nicotinamide riboside (which has gained popularity over the past couple of years). Oral supplements have to battle the digestive system, resulting in limited absorption and nutrient delivery to cells. Intravenous NAD+ therapy is the most effective way to increase NAD+ levels because it bypasses the digestive tract.
Before the experiment, scientists found low levels of NAD+ in older mice and also higher PARP1-DBC1 complexes. This information suggests that PARP1 is unable to repair DNA damage. After NMN supplementation, NAD+ concentrations were higher. There was also increased activity of PARP1, indicating NAD+ plays a critical role in PARP1 activity.
“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,” said Sinclair.
Within the same study, mice were exposed to radiation to determine NMN’s protective effect. Sinclair found that treatment before and after exposure to NMN reduced DNA damage. Amazingly, it also reduced the damaging effects on white blood cell count, lymphocyte count, and hemoglobin levels. Sinclair’s next project will be launching a similar study with 25 human subjects within the next six months, similar to the human applications that have been conducted by our team over the past eleven months at the NAD Treatment Center, so stay tuned for further updates.
NAD+ is known to decrease with age and this may limit the cell’s ability to repair itself. These studies show that NAD+ supplementation can be an effective way to protect against DNA damage, and possibly reverse the signs of aging. So, go ahead and make that birthday wish. More candles on the cake aren’t necessarily a bad thing when science is on your side.