NAD+

• NAD+ is best thought of as a support molecule that is essential to cellular metabolism as well as extracellular communication. Research shows that NAD+ plays important roles in energy conversion, DNA repair, immune defense, and circadian cycles. Levels of the cofactor, however, are sensitive to disease state as well as age. NAD+ as the following effects that decline as a result of natural age-related decreases in the levels of the cofactor.
• NAD+ activates sirtuins and other enzymes, liked Poly-ADP-ribose polymerases, involved in DNA repair and inflammatory processes. Sirtuins are the same enzymes linked to the life-extending benefits of calorie restriction.
• NAD+ controls the production of the protein PGC-1-alpha, which protects neurons and other cells in the central nervous system from oxidative stress. Research in mice shows that this particular effect may be linked to improved memory, particularly with aging.
• In mouse models, NAD+ helps to protect blood vessels against age-related hardening and the deposition of atherosclerotic plaques. In some studies, the cofactor even helps to reverse age-related dysfunction of the aorta.
• Mice given NAD+ show increased rates of metabolism and improved lean body mass.
• Increased NAD+ levels can increase muscle strength and endurance in older mice.
• NAD+ has been linked to extracellular signaling, particularly for smooth muscle. It may be of benefit in GI function. This effect is likely responsible for NAD+ benefits on blood pressure[1], [2].

• Vitamins B1, B2, and B6 help to boost NAD+ salvage. When combined with NAD+ supplementation, they may help to improve overall NAD+ levels.

One of the primary results of the standard aging process is a decline in both the quality and activity of mitochondria. Mitochondria are the body’s power plants, producing the energy for everything from neuron firing to digestion and muscle function. A decline in mitochondrial functioning has been associated with normal aging, but is also a factor in a number of age-related disease processes. Research shows that mitochondrial aging contributes to cellular senescence, inflammation, and even changes in stem cell activity that reduce rates of healing and make it harder for the body to recover from injury in old age[5].

” In other words, mitochondria are the lynch pin of cellular aging and understanding how to protect their function is a necessary first step in understanding how to slow, stop, or even reverse the aging process.

Research completed in 2013 showed that declining levels of NAD+ leads to a pseudohypoxic state within cells. This, in turn, interrupts the normal signaling that takes place between the nucleus, where DNA resides, and the mitochondria. By supplementing old mice with NAD+, mitochondrial function is restored and the communication commences again[7].

Source: PubMed

Research shows that exercise training actually has the same effects on aging mitochondria as NAD+ supplementation does. It appears that, in both cases, intervention helps to prevent changes in peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1-alpha) signaling that lead to mitochondrial dysfunction[10].

Research in mouse models of skeletal muscle aging suggests that exercise training helps to maintain muscle oxidative capacity over a lifetime. At least part of the reason that this works is that exercise increases PGC-1-alpha levels, which in turn helps to protect mitochondrial DNA, oxidative proteins, and angiogenic (blood vessel stimulating) proteins[11].