NAD+

NAD+ (Nicotinamide Adenine Dinucleotide) is a coenzyme present in every living cell, functioning as a critical electron carrier in cellular metabolism. In its oxidised form (NAD+), it accepts electrons from metabolic reactions; in its reduced form (NADH), it donates them to the electron transport chain for ATP production. This redox cycling is fundamental to energy metabolism — without NAD+, cells cannot convert food into usable energy.

Beyond energy metabolism, NAD+ serves as a substrate (not just a cofactor) for three major enzyme families: sirtuins (SIRT1-7), poly-ADP-ribose polymerases (PARPs), and CD38/CD157 ectoenzymes. Sirtuins are NAD+-dependent deacetylases that regulate gene expression, DNA repair, mitochondrial biogenesis, and inflammatory pathways — they are central to current theories of biological aging. PARPs consume NAD+ to repair DNA damage, and CD38 uses NAD+ in immune cell signalling.

The critical insight driving NAD+ research is that cellular NAD+ levels decline by approximately 50% between ages 40 and 60. This decline impairs sirtuin and PARP activity, leading to reduced DNA repair capacity, mitochondrial dysfunction, chronic inflammation (inflammaging), and metabolic decline. Replenishing NAD+ levels is therefore a primary target of geroscience research.

NAD+ was discovered in 1906 by Arthur Harden and William Young during their studies of yeast fermentation, making it one of the oldest known biological molecules. Hans von Euler-Chelpin received the Nobel Prize in Chemistry in 1929 for elucidating its role in fermentation, and subsequent Nobel-winning work by Otto Warburg (1931) and Arthur Kornberg (1959) further characterised its metabolic functions.

The modern era of NAD+ research was catalysed by the discovery of sirtuins in the early 2000s. David Sinclair at Harvard Medical School demonstrated that declining NAD+ levels drive age-related metabolic dysfunction, and that replenishing NAD+ could reverse certain markers of aging in animal models. This work — published in landmark papers in Cell (2013) and Science (2017) — launched a global research effort into NAD+ biology and its therapeutic potential for aging, neurodegeneration, and metabolic disease.