Treatment with NAD+ precursors improve wound healing in diabetic and old mice

Das A1,2, Giatsidis G2, Garg N2, Wu L1, Orgill D2 and Sinclair D1,2

  1. University of New South Wales, Sydney.
  2. Harvard Medical School, USA.

Delayed wound healing is one of the major complications in diabetes and ageing, which may result in limb amputation. Recent reports suggest that Sirtuins, a family of NAD+-dependent protein deacylases, play an important role in skin wound healing in both diabetes and ageing. Transgenic mice systemically overexpressing SIRT1, the mammalian sirtuin orthologue, showed improved skin wound healing in old and diabetic mice. The activity of SIRT1 is dependent on the levels of NAD+ inside the cell. The NAD+levels however decrease in different tissues with ageing and diabetes, resulting in declining SIRT1 activity. Boosting the levels of NAD+ using NAD+ boosters is emerging to be an effective strategy to activate and reproduce the effects of Sirtuins in ageing and diabetes. Here, we tested the efficacy of two NAD precursors – Nicotinamide riboside (NR) and Nicotinamide Mononucleotide (NMN) – in wound healing in old and diabetic mice. Topical administration of both of these compounds resulted in enhanced wound healing, increased wound vascularity, and significant improvement in the ischemic neovascular response. These findings have implications to significantly improve quality of life of diabetic patients and ageing population who have severely impaired wound-healing capabilities after injuries.