A Discovery in Longevity: Potential Elixir of Life?

By David Hong ’19

In our daily lives, exposure to the sun or similar small doses of radiation causes DNA damage in our cells, but our bodies have a very efficient system to repair this damage. On March 24th, research teams at Harvard Medical School and the University of New South Wales collectively published findings that could potentially prevent DBC1 inhibition and reverse aging and radiological damage.

To elaborate on this specific DNA repair mechanism, poly (adenosine diphosphate-ribose) polymerase 1, or PARP1, floats around in the cell and detects single-stranded break damages in the DNA. When it is detected, PARP1 binds with the damaged site and recruits the necessary proteins to remodel the broken part. Once it finishes, PARP1 and the proteins break out of the site and repeats this process for about a million items per day in a cell.

The research team found that, as we grow older, the efficiency of this process deteriorates because our body produces less nicotinamide adenine dinucleotide (NAD), which is primarily known for its critical role in converting energy in human respiration. More importantly, NAD binds with Deleted in Breast Cancer-1 (DBC1). Without sufficient concentration of NAD, DBC1 would interact and bind with PARP1, preventing PARP1 from recovering DNA defects. The team hypothesized that increased level of NAD will reduce the likelihood of DBC1 interfering with the functionality of PARP1, thereby increasing the capacity of DNA repair against aging or exposure to radiation.

The researchers examined the effects of increased concentration of NAD on the DNA recovery capabilities by conducting experiments on young and old, irradiated and controlled mice. By supplementing nicotinamide mononucleotide (NMN), which is then converted to NAD, the amount of DNA damage is reduced especially for the older and irradiated mice. In fact, middle-aged mice with NMN lived 20 to 35 percent longer than their life expectancy. Dr. Lindsay Wu, one of the researchers who participated in this study, expected that they could start human trials within six months.

This discovery has extensive and productive applications. NASA has been co-funding the research team, believing that NMN supplements could potentially reduce the side effects of radiation exposure for astronauts. Two of the researchers, Dr. Wu and Professor Sinclair, have biotech companies that are developing the NMN drug substance. This could be the key to prevent cancer and numerous aging-associated diseases such as type-2 diabetes, Alzheimer’s, hypertension, and cardiovascular diseases. In response to demographic aging, Japan has already funded a similar experiment conducted by Keio University in Japan which also showed improved life expectancy of mice and started human trials in October 2016.

Dr. Wu claims that his NMN supplements would be available by 2020. Until then, we can consume broccoli, cucumber, and avocado which have small doses of NMN and wait to see if NMN supplements truly become the elixir of life.








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