Mitochondria are fascinating structures within the cells. These tiny organelles, also called the powerhouses of cells, create energy through a process of oxidative phosphorylation. It is a process where nutrients from the food such as fatty acids, carbohydrates and amino acids are processed and undergo a series of complex bio-chemical reactions in the mitochondria to generate ATP. ATP is the energy currency used by the cells to power a wide range of functions. Mitochondria are self-contained and even have their own DNA, known as mitochondrial DNA.
Mitochondria have many important roles in addition to energy production. These amazing structures help to maintain metabolic balance in the body and determine how a cell would survive in the face of stress. They can modify their concentration and functions in response to the fluctuating shifting energy requirements of the cells. If a cell needs more energy, mitochondria multiply. This means energy-hungry cells would essentially have more mitochondria than the cells that don’t require as much energy. For example, an exercising muscle will spur the production of more mitochondria to keep pace with increased energy demand.
NAD+ and Mitochondrial Fitness
NAD+ is an important player in the energy creation process within the mitochondria. NAD+ also enables the communication within the cell between the nucleus and its mitochondria. Recent studies suggest that cells increase the synthesis of NAD+ in response to mild stress, including calorie restriction.
However, as we age NAD+ levels in the body takes a hit. Besides age, there are other factors that lead to depleting levels of this co-enzyme, namely excessive eating and inactive lifestyle. In addition, there are many proteins that compete for the same NAD+ pool within the nucleus. For example, Sirtuins family of enzymes, Poly-ADP-ribose Polymerases (PARPs) and CD38 all require NAD+ as a substrate to perform their many critical functions.
Focusing especially on Sirtuins, these NAD + dependent proteins play key roles in how cells respond to changes in nutritional and environmental changes, for example fasting, DNA damage and oxidative damage. NAD+ activates the Sirtuins that improve metabolic efficiency and also “upregulate mitochondrial oxidative metabolism and the accompanying resistance to oxidative stress.” Recent studies suggest that decline in NAD+ levels may cause aging through “decreased Sirtuin activities in the nucleus and mitochondria .”
Low NAD+ levels and mitochondrial dysfunction
Low levels of NAD+ causes mitochondria to dysfunction, which can lead to reduction in ATP production, abnormal production of free radicals and the resulting oxidative damage, cell apoptosis, inadequate DNA repair, and metabolic imbalance. These major factors are involved in the process of aging and in the gradual onset of many age-associated pathologies such as diabetes, cardiovascular disease, Alzheimer’s disease, arthritis and cancer.
To avoid these degenerative conditions, it is important to maintain optimum NAD+ levels in the body. Calorie restriction (limited intake of calories) is one proven technique to naturally achieve increased intracellular levels of NAD+. However, it is not practical and not possible to implement on a day to day basis. Another effective method to restore NAD+ levels within the body is to take NAD+ supplements.
- Imai et al. NAD+ and Sirtuins in Aging and Disease. Trends in Cell Biology. 2014.