Age-Associated Changes In Oxidative Stress & NAD+ Metabolism In Human Tissue

Age-Associated Changes In Oxidative Stress & NAD+ Metabolism In Human Tissue

Published in PLOS One.

We need NAD+ in our cells to make an enzyme called PARP, which fights oxidative damage and helps keep our DNA in good repair. We also need NAD+ to support the activities of enzymes called sirtuins, the so-called “longevity enzymes”. It’s been established in rodents that there are links between age-related DNA damage, PARP-facilitated NAD+ depletion and lack of sirtuin activity. In this study, investigators wanted to see if these same associations were present in aging human tissue.

Skin samples were taken from consenting patients, ages 0-1 and 17-77 years, during previously scheduled, unrelated surgical procedures. There were several important findings:

  • There was a strong link between increasing age and DNA damage in both males and females.
  • In males, there was a significant increase in PARP activity with age, and it was linked to a decrease in NAD+ levels in their tissues. This association was less evident in females.
  • In both males and females, NAD+ levels declined with age.
  • Sirtuin activity declined with age in males but not in females.
  • There was a strong link between oxidative stress and DNA damage in post-adolescent males. There was also a strong link between increased PARP activity and NAD+ levels in this group.

This study provides measurable evidence that when we age, and our bodies produce a lot of extra PARP due to accumulated oxidative damage to our DNA, this may result in reduced levels of NAD+ in our tissues. These lower NAD+ levels may play a major role in the aging process by limiting energy production, DNA repair and other important communications between cells.

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