What is NAD+? A plain-English guide to the cell’s busiest coenzyme

Few molecules are mentioned as often in the biology of ageing as NAD+. It turns up in discussions of energy, mitochondria, DNA repair and the slow changes that come with age. Yet it is rarely explained in plain terms. This guide sets out what NAD+ actually is, the jobs it does inside every cell, the observation that its levels fall as we grow older, and what the research does and does not establish. The aim is a calm, evidence-first picture rather than a list of promises.

What NAD+ actually is

NAD+ is short for nicotinamide adenine dinucleotide, and it is a coenzyme found in every living cell. A coenzyme is a small helper molecule that enzymes rely on to do their work. NAD+ is among the most abundant and most widely used of these helpers, which is why it appears in so many different processes at once. It exists in two interconvertible forms, an oxidised form written as NAD+ and a reduced form written as NADH, and the cell constantly shifts between the two. A 2021 review in Nature Reviews Molecular Cell Biology describes NAD+ as a central hub of cellular metabolism, a molecule that sits at the meeting point of energy production and a wider set of signalling roles.

Its role in energy metabolism

The most established job of NAD+ is in energy metabolism, where it acts as a redox carrier. In plain terms, it shuttles electrons from one reaction to another. As the cell breaks down nutrients from food, NAD+ accepts electrons and becomes NADH. That NADH then delivers its electrons to the mitochondria, the structures often described as the cell’s power plants, where they help drive the production of the cell’s main energy currency. The NAD+ is then regenerated and the cycle repeats. This continuous flow between NAD+ and NADH is fundamental to how cells extract usable energy from what we eat, and a 2020 review in Signal Transduction and Targeted Therapy sets out how central this redox role is to normal cellular function.

Beyond energy: a molecule that gets used up

For a long time NAD+ was thought of mainly as the redox carrier described above. The picture has since broadened. NAD+ is not only passed back and forth in energy reactions, it is also consumed as a raw material by several families of enzymes. Three are studied most closely. The sirtuins, a group of enzymes linked to the regulation of many cellular processes, use NAD+ as they work. The PARPs, enzymes heavily involved in detecting and repairing damaged DNA, also draw on NAD+. And an enzyme called CD38, which becomes more active in certain conditions, consumes NAD+ as well. Because these enzymes break NAD+ down rather than simply borrowing it, the cell must keep making more. This consuming role places NAD+ at the heart of DNA repair and of the signalling that helps cells respond to stress and damage, a point emphasised in a 2024 article in Cold Spring Harbor Perspectives in Medicine.

Why levels appear to fall with age

One of the observations that has drawn so much attention to NAD+ is that its levels appear to decline with age across a range of tissues. The proposed explanation is a shift in balance. On one side is synthesis, the cell’s ongoing production of NAD+ from dietary precursors and recycled building blocks. On the other is consumption, the demand from the sirtuins, the PARPs, CD38 and the redox reactions of metabolism. A 2021 review in Mechanisms of Ageing and Development frames ageing-related NAD+ decline as exactly this kind of imbalance, with consumption tending to rise, in part through greater activity of enzymes such as CD38 and through accumulating DNA damage, while synthesis does not keep pace.

It is worth being careful here. Measuring NAD+ accurately in living tissue is technically difficult, levels vary between tissues and over the course of a day, and much of the human data comes from blood rather than the organs of greatest interest. So the broad pattern of decline is well supported, but the precise size and significance of the fall in any given tissue is harder to pin down. The measurement caveats are real and are acknowledged across the literature.

Why this became such a busy research area

The reason NAD+ has become a busy field is the chain of reasoning that connects these threads. NAD+ supports energy production. It fuels the sirtuins and the DNA-repair machinery. Its levels fall with age. Several features of ageing involve declining energy metabolism and accumulating damage. Put together, this raises an obvious question: does falling NAD+ help drive aspects of ageing, and could supporting it make a difference? A 2023 review in Aging Cell examines the links between NAD+ metabolism and the way cells age, including its connections to the senescent state. The interest is genuine and the biology is plausible. What remains open is causality. An association between lower NAD+ and ageing does not by itself show that the decline is a cause rather than a consequence, and untangling the two is an active area of work.

What is established and what is uncertain

It helps to separate the settled science from the open questions. Established: NAD+ is an essential coenzyme present in every cell, it is central to redox reactions in energy metabolism, and it is consumed by the sirtuins, the PARPs and CD38 in processes that include DNA repair and signalling. Also reasonably well supported: NAD+ levels tend to fall with age in many tissues, driven by a shifting balance between synthesis and consumption. Less certain: precisely how much NAD+ falls in specific human tissues, how much of the decline is cause versus consequence of ageing, and what the long-term consequences of attempting to influence NAD+ levels in humans might be. The honest summary is that NAD+ is one of the most interesting molecules in the biology of ageing, that the foundational biochemistry is solid, and that several of the most eye-catching claims still rest on animal work and early human data. It is a field to follow with curiosity and patience rather than certainty.

Further reading

Continue reading from the journal: Mitochondrial biology: what changed in 2025, The hallmarks of cellular ageing, in plain English and NMN clinical trials: a sober reading of the human evidence.

Sources

• Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 2021. doi:10.1038/s41580-020-00313-x
• Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, Li C, Shen G, Zou B. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy, 2020. doi:10.1038/s41392-020-00311-7
• Strømland Ø, Diab J, Ferrario E, Sverkeli LJ, Ziegler M. The balance between NAD+ biosynthesis and consumption in ageing. Mechanisms of Ageing and Development, 2021. doi:10.1016/j.mad.2021.111569
• Chini CCS, Cordeiro HS, Tran NLK, Chini EN. NAD metabolism: role in senescence regulation and aging. Aging Cell, 2023. doi:10.1111/acel.13920
• Lautrup S, Hou Y, Fang EF, Bohr VA. Roles of NAD+ in Health and Aging. Cold Spring Harbor Perspectives in Medicine, 2024. doi:10.1101/cshperspect.a041193