In short
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme present in every cell that is essential for energy metabolism and serves as a required cofactor for sirtuins and PARP enzymes involved in DNA repair.
NAD+ shuttles electrons in redox reactions central to glycolysis, the citric acid cycle, and oxidative phosphorylation, making it indispensable for ATP production. Beyond metabolism, NAD+ is consumed (not just used catalytically) by two other enzyme families: sirtuins, which use it for protein deacetylation, and PARPs (poly-ADP-ribose polymerases), which use it for DNA damage repair. Because both compete for the same NAD+ pool, DNA damage that activates PARP can deplete NAD+ available for sirtuin activity.
Human tissue studies have measured a decline in NAD+ levels with age, attributed to a combination of reduced synthesis and increased consumption — notably by CD38, an enzyme whose activity in immune cells rises with age and chronic inflammation, degrading NAD+ in the process. This age-related decline is the central rationale for supplementing with NAD+ precursors like NMN and NR, which the body converts into NAD+ through the salvage pathway, since NAD+ itself is not efficiently absorbed orally.
Human trials of NMN and NR have generally shown these precursors do raise blood NAD+ levels reliably, and some small trials report modest improvements in specific biomarkers (such as some measures of insulin sensitivity or muscle-related markers in specific populations). No trial has demonstrated that raising NAD+ levels extends human lifespan or reverses a hallmark of aging in humans — the evidence to date is precursor pharmacokinetics and early-stage biomarker signals, not a proven aging-reversal therapy.
Worth remembering
- Essential coenzyme for energy metabolism and a required cofactor for sirtuins and PARP DNA-repair enzymes.
- NAD+ levels decline with age, partly due to increased breakdown by CD38.
- NMN/NR reliably raise blood NAD+ in humans; no trial shows this extends lifespan.