Supplements of the drug NAD+ may offer a new way of attacking Werner Syndrome, according to a study with animal models.
“We are showing for the first time that Werner Syndrome is due to errors in the clean-up process. When we improve the clean-up by giving supplements of the drug NAD+, we can show in animal models that it increases lifespan and delays the aging processes,”
says Vilhelm Bohr, a professor at the Center for Healthy Aging, the University of Copenhagen, and the National Institutes of Health, who led the study.
Patients with Werner Syndrome have early signs of aging, such as grey hair, wrinkled skin, and increased incidence of cancer and type 2 diabetes. On average, they die at the age of 45. The underlying mechanisms of the disease are unknown and therefore, no treatment is yet available.
The researchers looked at a clean-up process in cells called mitophagy that breaks down defective mitochondria and reuses the proteins of which they’re made.
[caption id=“attachment_101684” align=“aligncenter” width=“700”] WRN mutation leads to cellular NAD+ reduction through the down-regulation of the NAD+ synthetic enzyme NMNAT1 and upregulation of cellular NAD+ consumption (e.g., by PARPs). Cellular NAD+ depletion impairs mitophagy through reduction of the activities of p-AMPK and p-ULK1, two upstream proteins which regulate autophagy/mitophagy. This results in accumulation of damaged mitochondria and impaired mitochondrial homeostasis.
Credit: Fang, E.F., et al. CC-BY[/caption]
In addition, they have also tested NAD+ in the animal models.
“It strongly reinforces our findings that the clean-up process seems to be important in both human cells and across different animals. And then it is encouraging that in living animals, we can improve lifespan and delay the aging processes which are the key symptoms of Werner Syndrome,”
Werner Syndrome is most common in Japan, where between 1 in 20,000 and 1 in 40,000 people have the disease. In the United States, it is 1 in 200,000.
“Our results are so promising that we have received inquiries from Japan with a view to performing clinical studies of patients with Werner Syndrome. We very much hope that the studies will point in the same direction so that patients can live longer and with a higher quality of life,”
The study also helps to understand the mechanisms of aging, as aging processes in patients with Werner Syndrome are similar to what you normally see, except that the aging happens significantly earlier. In the long term, the new knowledge could also help to delay the normal aging of the body and improve the quality of life in old age.
 Fang, E.F., Hou, Y., Lautrup, S. et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun 10, 5284 (2019) doi:10.1038/s41467-019-13172-8