Tissue‐specific effects of exercise as NAD⁺‐boosting strategy: Current knowledge and future perspectives

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an evolutionarily highly conserved coenzyme with multi‐faceted cell functions, including energy metabolism, molecular signaling processes, epigenetic regulation, and DNA repair. Since the discovery that lower NAD+ levels are a shared characteristic of various diseases and aging per se, several NAD+‐boosting strategies have emerged. Other than pharmacological and nutritional approaches, exercise is thought to restore NAD+ homeostasis through metabolic adaption to chronically recurring states of increased energy demand. In this review we discuss the impact of acute exercise and exercise training on tissue‐specific NAD+ metabolism of rodents and humans to highlight the potential value as NAD+‐boosting strategy. By interconnecting results from different investigations, we aim to draw attention to tissue‐specific alterations in NAD+ metabolism and the associated implications for whole‐body NAD+ homeostasis. Acute exercise led to profound alterations of intracellular NAD+ metabolism in various investigations, with the magnitude and direction of changes being strongly dependent on the applied exercise modality, cell type, and investigated animal model or human population. Exercise training elevated NAD+ levels and NAD+ metabolism enzymes in various tissues. Based on these results, we discuss molecular mechanisms that might connect acute exercise‐induced disruptions of NAD+/NADH homeostasis to chronic exercise adaptions in NAD+ metabolism. Taking this hypothesis‐driven approach, we hope to inspire future research on the molecular mechanisms of exercise as NAD+‐modifying lifestyle intervention, thereby elucidating the potential therapeutic value in NAD+‐related pathologies.

Muscle physiology and its relations to the whole body in health and disease

“…Exercise training elevated NAD + levels and NAD + metabolism enzymes in various tissues. 23 As mentioned above, physical exercise causes small injuries in muscle fibres, which induces regenerative processes. In a recent study, they tried to support the regeneration of collagen-rich extracellular matrix of tendon tissue by oral supplementation and showed that remodeling of skeletal muscle by resistance training can be supported by supplementation of bioactive collagen peptides.…”

“…Exercise modality, cell type, and investigated animal model or human population strongly influence the extent and direction of changes. Exercise training elevated NAD + levels and NAD + metabolism enzymes in various tissues 23 …”

Boosting the Exhausted Vasculature—SIRT3 (to the) Rescue

“…Oral supplementation with nicotinamide, an NAD + precursor, normalized myocardial metabolism and function, lowered blood pressure, and improved mortality in animal models of heart failure ( 17 ). It is intriguing that certain exercise regimes were associated with tissue-specific increases in NAD + levels ( 18 ). A well-balanced and controlled level of physical activity through regular exercise was also shown to be beneficial for patients with PH ( 19 ).…”