SIRT1, NAD+ and Aging
The SIRT1 complex is a critical nuclear signaling molecule that regulates the health and proper functioning of our mitochondria. NAD+ is the main cofactor in SIRT1 enzyme complex . The majority of the genes responsible for the creation of the component parts of the electron transport chain are encoded in the nucleus of the cell . Here NAD+, along with SIRT1, play a critical role in that they are responsible for the turning on of the very genes that encode the protein complexes that make up the ETC .
As we age the pool of available NAD+ diminishes and so does the effectiveness of SIRT1. With SIRT1 functioning at lowered capacity, the gene signaling and subsequent ETC complex production go down. With lowered ETC functioning, fewer ATP is produced and energy levels throughout the body go down. At the same time, more ROS (reactive oxygen species) are produced which accelerate cell damage and decay. The mitochondria begin to die off and eventual total cell death occurs.
New studies on raising NAD+ levels show that this process of cell degeneration and eventual death can be reversed by increasing the available nuclear NAD+ pool. A recent mouse study conducted by Dr. Patricia Gomes of Harvard University showed that the negative effects of decreased mitochondrial functioning could be reversed with the one-week oral administration of NMN, a precursor to NAD+ in the body . Interestingly, calorie restriction also increased NAD+ and SIRT1 activity and showed similar effects at reversing the damage to the mitochondrial ETC .
Oral supplementation with NAD+ and NAD+ precursors upregulates SIRT1 activity and reverses mitochondrial damage (and subsequent ROS production), which are the key drivers of cellular aging and death. Currently, the most convincing studies in this area are being conducted in mice, but clinical human use of oral NAD+ supplementation confirms more globally all the positive effects noted in these mouse studies. Patients reporting increased energy, stamina, and feelings of well being, and decreases in fatigue and muscle soreness all correlate with these preliminary animal studies.
With the passage of time, aging is something that all life on earth experiences. However, with new advances in science from the mitochondrial theories of aging and the use of NAD+ supplementation to strengthen and support our mitochondrial health, perhaps we can increase our longevity and lead longer, healthier, more fit lives long into the future.