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

Borut Poljsak,Vito Kovač,Irina Milisav,Jonathan N Myers

doi:10.1155/2020/8819627

Borut Poljsak, Vito Kovač + Show 2 more

Open Access

https://doi.org/10.1155/2020/8819627

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Abstract

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.

Highlights

Fasting, caloric restriction, sports activity, low glucose availability, and heat shocks are lifestyle and nutrition approaches that influence NAD+ levels [1,2,3,4,5,6]
Caloric restriction reduces NADH amount more than it influences the NAD+ levels, at least in yeast [54, 60]. It seems that lowering NADH is an important factor responsible for the increased activity of the nicotinamide adenine dinucleotide- (NAD+-)consuming enzymes, as NADH is an inhibitor of Sirtuins and PARPs [54]
Both exercise and caloric restriction trigger the metabolic stress that follows by adaptation by inducing NAMPT expression through the AMPK [4, 109, 114] resulting in increased NAD+ levels available for sirtuins and PARPs

Summary

Introduction

Caloric restriction, sports activity, low glucose availability, and heat shocks are lifestyle and nutrition approaches that influence NAD+ levels [1,2,3,4,5,6]. NAD+ is a rate-limiting substrate for many signalling enzymes such as sirtuin (SIRT) proteins SIRT1 and SIRT3, the poly (ADP-ribose) polymerase (PARP) proteins PARP1 and PARP2, a COOH-terminal binding protein (CtBP), cyclic ADP-ribose (ADPR) synthetases CD38 and CD157, and many other NAD+-dependent enzymes These enzymes are involved in important cellular processes, like DNA repair, stress response, genomic stability, chromatin remodelling, circadian rhythm regulation, cell cycle progression, insulin secretion and sensitivity, and expression of the inflammatory cytokines, translating changes in energy status into metabolic adaptations [12]. Caloric restriction reduces NADH amount more than it influences the NAD+ levels, at least in yeast [54, 60] It seems that lowering NADH is an important factor responsible for the increased activity of the NAD+-consuming enzymes, as NADH is an inhibitor of Sirtuins and PARPs [54]. CD38, its homologue CD157, and PARP-1 inhibitors could increase NAD+ availability; they are registered as medical drugs for cancer treatment [24], beyond the scope of this review

Eating Habits

Environmental Stress

Findings

Conclusions