Maintaining healthy tissue and cellular turnover is crucial for overall balance in the body and for healing from injuries. Stem cells play a key role in this process by replenishing and transforming into different cell types. However, as we age, stem cells lose their ability to multiply and change into other cells, leading to tissue breakdown.

Calorie restriction (CR) is a method that helps maintain the function and health of stem cells as we grow older. It works by activating protective stress response pathways, such as the sirtuins enzymes, which are important for cellular adaptations to CR. These enzymes rely on a co-substrate called NAD+ for their activity. However, NAD+ levels decline as we age, which reduces the effectiveness of these enzymes.

Another protective pathway against aging is the mitochondrial unfolded protein response (UPRmt). This pathway helps protect mitochondria, the energy-producing organelles in cells, from stress. One trigger for the UPRmt is an imbalance in the components of the mitochondrial electron transport chain (ETC), which is necessary for cellular respiration. Activation of the UPRmt can extend lifespan.

Recent research has shown that replenishing NAD+ levels using a precursor called nicotinamide riboside (NR) can reverse stem cell dysfunction in aged mice. This treatment improved mitochondrial function in stem cells, allowing them to better replicate and transform into mature cells. This led to enhanced physical performance and improved muscle repair in older mice, as well as increased neurogenesis.

At the molecular level, NR treatment activates a protein complex called prohibitins, which are involved in the UPRmt pathway. This suggests that the beneficial effects of NR on stem cells are mediated through this pathway. However, it’s unclear whether epigenetic changes also play a role in this process.

Furthermore, NR treatment has been shown to extend lifespan in mice, although it’s not yet clear if this is directly linked to the rejuvenation of stem cells. Nonetheless, restoring NAD+ levels through metabolic precursors like NR holds promise for improving overall health in old age, suggesting potential for future therapeutic interventions.

Call or Text WestCoast IV at (858) 255-0699 for any questions about NAD+ Infusions.

References Gomes AP, Price NL, Ling AJ, et al. Cell 2013; 155:1624–1638. Oberdoerffer P, Michan S, McVay M, et al. Cell 2008; 135:907–918. Durieux J, Wolff S, Dillin A . Cell 2011; 144:79–91. Zhao Q, Wang J, Levichkin IV, et al. EMBO J 2002; 21:4411–4419. Yoneda T, Benedetti C, Urano F, et al. J Cell Sci 2004; 117:4055–4066. Houtkooper RH, Mouchiroud L, Ryu D, et al. Nature 2013; 497:451–457. Mouchiroud L, Houtkooper RH, Moullan N, et al. Cell 2013; 154:430–441. Zhang H, Ryu D, Wu Y, et al. Science 2016; 352:1436–1443. https://www.nature.com/articles/cr201680