Borut Poljsak
Abstract
Oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) is currently intensively investigated topic in longevity science. However, if ageing is considered a defense mechanism against cancer, caution should be implemented regarding the use of NAD+ and its precursors. In the hypothesis presented NAD+ is shown as an important factor related to cancer formation and prevention. NAD+ depletion with age may play a major role in the process of cancer formation by limiting (1) energy production, (2) DNA repair, (3) genomic stability and signaling. Disruption of any of these processes could increase the cancer risk due to impaired genomic stability. NAD+ content is a critical protective factor in early carcinogenesis and can become detrimental factor later in cancer progression and promotion phase. Namely, NAD+ restoration could prevent or reverse the phenotype of malignant cells at early stages by inducing cellular repair and stress adaptive response as well as regulate cell cycle arrest and apoptotic removal of damaged cells. Contrary, during cancer promotion, progression and treatment increased NAD+ levels could have deleterious effects on the malignancy process due to growth advantage, increased resistance and greater cell survival. NAD+ levels can be increased with exercise, caloric restriction and ingestion of NAD+ precursors and intermediates or could be increased by using PARP and CD 38 inhibitors. The evidence indicating that modulation of NAD+ levels could be important in cancer prevention, initiation and progression phase is presented.
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