Healthy Lifestyle Recommendations: Do the Beneficial Effects Originate from NAD+ Amount at the Cellular Level?

In this review, we describe the role of oxidized forms of nicotinamide adenine dinucleotide (NAD(+)) as a molecule central to health benefits as the result from observing selected healthy lifestyle recommendations. Namely, NAD(+) level can be regulated by lifestyle and nutrition approaches such as fasting, caloric restriction, sports activity, low glucose availability, and heat shocks. NAD(+) is reduced with age at a cellular, tissue, and organismal level due to inflammation, defect in NAMPT-mediated NAD(+) biosynthesis, and the PARP-mediated NAD(+) depletion. This leads to a decrease in cellular energy production and DNA repair and modifies genomic signalling leading to an increased incidence of chronic diseases and ageing. By implementing healthy lifestyle approaches, endogenous intracellular NAD(+) levels can be increased, which explains the molecular mechanisms underlying health benefits at the organismal level. Namely, adherence to here presented healthy lifestyle approaches is correlated with an extended life expectancy free of major chronic diseases.