NAD⁺: what it does in the cell

What NAD⁺ is

Nicotinamide adenine dinucleotide (NAD⁺) is a coenzyme present in every living cell. It works as a molecular shuttle, carrying electrons between metabolic reactions, and it sits at the center of how cells generate energy and maintain themselves.

Core functions

Electron transport and energy generation

NAD⁺ cycles between its oxidized form (NAD⁺) and its reduced form (NADH), taking part in redox reactions across glycolysis, the citric acid cycle, and oxidative phosphorylation. Those pathways produce ATP, the cell's primary energy currency.

Substrate for repair and signaling enzymes

NAD⁺ is consumed as a substrate by two important enzyme families: sirtuins, a class of deacetylases associated with metabolic regulation, and PARP enzymes, which participate in DNA repair. Because these enzymes use NAD⁺ rather than simply recycling it, cellular NAD⁺ availability is tied to genomic stability and stress response.

Circadian regulation

NAD⁺ synthesis follows a daily rhythm, and NAD⁺-dependent sirtuin activity feeds back into the circadian clock. The coenzyme therefore sits at an intersection between metabolism and circadian timing.

Decline with age

Tissue NAD⁺ levels decline with age across multiple model organisms and in human tissue. That decline has been associated with reduced mitochondrial function, diminished sirtuin activity, and increased DNA damage — though whether it is a cause or a consequence of aging remains an open question in the literature.

Precursor pathways

Cells synthesize NAD⁺ through several routes, including salvage pathways that recycle nicotinamide. Two precursors have drawn particular research attention:

• Nicotinamide mononucleotide (NMN)
• Nicotinamide riboside (NR)

Both are converted to NAD⁺ within cells, and both have been studied in animal models for effects on mitochondrial function and markers of aging. Human data remains considerably more limited than the animal literature, and researchers generally describe the field as early.

Overview

Further reading

• Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD⁺ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. 2021;22(2):119–141. PubMed
• Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metabolism. 2018;27(3):529–547. PubMed

This article is a summary of published biochemistry and is informational only.