The role of exercise in modulating NAD+ metabolic enzymes: mechanisms and health benefits.

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme in cellular metabolism, acting as a substrate for NAD+-dependent enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs), and CD38, which are involved in essential cellular processes including DNA repair, gene expression, and mitochondrial function. Exercise has been identified as a potent modulator of NAD+ metabolism and also influencing the expression and activity of enzymes involved in NAD+ biosynthesis and consumption. Our review focuses on the molecular mechanisms through which exercise regulates NAD+ metabolic enzymes, more in relation to aerobic and resistance exercise. Evidence indicates that exercise enhances the activity of key enzymes, such as nicotinamide phosphoribosyltransferase (NAMPT) and sirtuins, thereby improving mitochondrial efficiency, oxidative metabolism, and cellular homeostasis. Additionally, exercise has also been shown to mitigate the age-related decline in NAD+ levels, offering a potential strategy for addressing metabolic dysfunctions and age-associated diseases. Despite these findings, the exact molecular pathways underlying the exercise-induced modulation of NAD+ metabolism remain unclear and require further investigation.