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Orange wheel that symbolizes N A D

NAD+

NAD+ (nicotinamide adenine dinucleotide) is a signaling molecule naturally present in every cell of the body and is critical for DNA repair, cellular energy production, and gene expression. (1,2) NAD+ levels naturally decline with age.

Conversely, increasing NAD+ levels may enhance physiological function and extend healthy human lifespan making repletion of this important molecule an essential target for age optimization.

Longevity Wheel with human outline and circles

Increasing Cellular NAD+

The most direct way to support NAD+ levels is to supplement the body with nicotinamide mononucleotide (NMN), a direct and stable precursor to NAD+. NMN is derived from vitamin B3, or nicotinamide.

Direct supplementation with NAD+ is ineffective for increasing systemic NAD+ levels due to the molecule’s propensity to break down in the gut. By comparison, NMN has a unique cellular transporter, Slc12a8, that facilitates direct uptake into cells. Once inside the cell, NMN is rapidly transformed into NAD+, repleting the body’s NAD+ pool. (8) Nicotinamide riboside (NR) is another NAD+ precursor popular in the longevity space; however, it must go through an additional metabolic step that converts it into NMN before entering cells.

NAD+ Metabolism Necessitates Methylation Support

Methylation is a biochemical process in which methyl (-CH3) groups are added to molecules within the body, impacting processes such as NAD+ metabolism.

Methylation keeps the NAD+ cycle running smoothly by removing excess NAM, an intermediate in the “Salvage Pathway,” a biochemical pathway that recycles NAD+.

When NAD+ levels increase in the body due to supplementation with NAD+ precursors such as NMN, excess NAM builds up and can inhibit the body’s ability to continue generating NAD+.

Trimethylglycine, riboflavin, and vitamin B12 are nutrients that provide methyl groups to methylate NAM, allowing it to be excreted. Simultaneous supplementation of methylation nutrients alongside NMN may thus optimize NAD+ bioenergetics, allowing you to experience the full potential of NMN supplementation.

The Role of NAD+ in Aging

Research is showing how influential NAD+ can be for longevity as it targets many key age management processes within the body, including:

Cellular energy production

NAD+ is found in the mitochondria of every cell of the body, except red blood cells, which do not harbor mitochondria. Inside the mitochondria, NAD+ carries high-energy electrons in the processes that create cellular energy (ATP), including glycolysis, the tricarboxylic acid cycle, and mitochondrial oxidative phosphorylation. A deficiency of cellular energy is associated with age-related health declines. (3)

Sirtuin regulation

NAD+ is a coenzyme for sirtuins, a crucial family of longevity-promoting proteins. SIRT1 pathways are believed to be the primary pathways through which NAD+ exerts longevity benefits.

CD38 regulation

NAD+ is also a cofactor for CD38, also known as “cyclic ADP ribose hydrolase.” CD38 is a glycoprotein found on the surface of many immune cells, including white blood cells. CD38 is a significant utilizer of NAD+ during the aging process because it is increased by the chronic inflammatory process characteristic of aging, referred to as “inflammaging.” (4,5)

PARP regulation

NAD+ is a cofactor for PARPs (poly ADP-ribose polymerase), a family of enzymes involved in DNA repair, the maintenance of genomic integrity, and programmed cell death. High levels of PARP activity to repair cellular damage can deplete NAD+.

Stem cell support

Restoration of healthy tissue levels of NAD+ may improve metabolic function in muscle, brain, and bone stem cells. (6,7) Stem cells are the “baby” cells of the body that allow tissues to regenerate themselves.

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