What Does NAD+ Do?
Energy metabolism: the classic role
NAD+’s original and best-characterized job is in cellular energy metabolism. As cells break down glucose and fat, NAD+ repeatedly accepts and donates electrons — cycling into NADH and back — at several steps of glycolysis, the citric acid cycle, and oxidative phosphorylation.[1][2] This electron-shuttling role is required for cells to generate ATP efficiently, and it has been established biochemistry for decades.
Sirtuins: NAD+-dependent regulators
Sirtuins are a family of enzymes that require NAD+ as a cofactor to function.[1][2] In cell and animal studies, sirtuins have been linked to processes such as metabolic regulation and cellular stress responses.[1] Much of the specific mechanistic detail here comes from cell-based and animal research; direct human evidence for how sirtuin activity translates into clinical outcomes is more limited, which is why a dedicated page later in this hub treats sirtuin biology on its own terms.
PARPs: NAD+ and DNA repair
PARPs (poly-ADP-ribose polymerases) are enzymes that use NAD+ as a substrate to help repair damaged DNA.[1][2] This is one of the main ways cells consume NAD+, particularly under conditions of DNA damage or cellular stress.[2] Like sirtuin biology, PARP activity is established biochemistry at the mechanistic level, with an actively developing picture of how it plays out across tissues and over a lifespan.
CD38 and other NAD+-consuming enzymes
CD38 is another enzyme that consumes NAD+, and it has been studied specifically in relation to age-related NAD+ decline in animal models.[3] A dedicated page on CD38 is planned for a later stage of this hub.
From biochemistry to biology: why this matters for aging research
Because NAD+ supports these processes, and because NAD+-related measurements tend to differ by age (covered on this hub’s page about NAD+ and aging), researchers have investigated whether raising NAD+ affects various physiological outcomes in humans.[1] It is important to be precise about what has and has not been shown: NAD+’s biochemical roles described above are well established; specific claims that raising NAD+ produces a defined human health benefit — more energy, better focus, slower aging — are a separate question, addressed with appropriate evidence grading elsewhere in this hub, not asserted here.
- NAD+'s role in energy metabolism is textbook, established biochemistry.
- NAD+ is also required by sirtuins and PARPs, enzyme families linked to DNA repair and cellular regulation.
- Most of what's known about sirtuin activation and downstream aging-related effects comes from cell and animal research; direct human evidence is still more limited.
- Nothing here should be read as a claim that raising NAD+ produces a specific, established human health benefit.
- 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. PMID: 33353981.
- Xie N, Zhang L, Gao W, et al. NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy. 2020. doi:10.1038/s41392-020-00311-7. PMID: 33028824.
- Hogan KA, Chini CCS, Chini EN. The Multi-faceted Ecto-enzyme CD38: Roles in Immunomodulation, Cancer, Aging, and Metabolic Diseases. Frontiers in Immunology. 2019. doi:10.3389/fimmu.2019.01187. PMID: 31214171.Primarily preclinical / mechanistic evidence on CD38.