NAD+ metabolism and its roles in cellular processes during ageing[1]
This comprehensive review examined the multiple enzymatic roles of NAD+ in aging biology, synthesizing evidence from cell culture, rodent, and human observational data. The authors documented the progressive decline of NAD+ concentrations -- approximately 50% between ages 20 and 60 -- and correlated this decline with reduced sirtuin deacetylase activity, impaired mitochondrial function, and accumulation of DNA damage. Key mechanistic findings included CD38 upregulation in aged tissues as a dominant driver of NAD+ consumption, and evidence that NAD+ precursor supplementation restored sirtuin activity and improved metabolic outcomes in aged mice. The review characterized NAD+ as a nexus molecule integrating energy metabolism, DNA repair, and circadian regulation.
Last verified: 2026-04-03
Sirtuin 1 (SIRT1) activation requires NAD+ as a substrate — structural and kinetic characterization[2]
This biochemical study provided kinetic and structural characterization of SIRT1's absolute dependence on NAD+ as a co-substrate for its protein deacetylase activity. Using purified recombinant SIRT1 and acetylated peptide substrates, the authors determined the Km for NAD+ to be approximately 170 uM under physiological conditions, meaning SIRT1 activity is sensitive to physiological fluctuations in NAD+ availability. Structural data confirmed that NAD+ occupies a conserved Rossmann fold and is cleaved at the nicotinamide-ribose bond during catalysis, releasing nicotinamide as a product inhibitor. These kinetic parameters establish the biochemical basis for the observed correlation between intracellular NAD+ levels and cellular aging phenotypes.
Last verified: 2026-04-03
