The sirtuin/nicotinamide adenine dinucleotide (NAD) system in human health and disease: inter-individual variation and modulation by diet and exercise

The sirtuin/ nicotinamide adenine dinucleotide (NAD) system is a diet sensor linked to healthy responses to stress. Sirtuins are key regulators of stress responses, regulating key processes intimately linked to maintenance of long-term health e.g. glucose and lipid homeostasis, inflammation and oxidative stress. Sirtuin function is dependent on the bioavailability of the cofactor NAD, a key molecule in cellular metabolism and respiration. NAD is biosynthesised from dietary sources of vitamin B3/niacin or the amino acid tryptophan, but can also be generated via salvage pathways that re-direct biosynthetic pathways to restore NAD within cells and tissues. The intrinsic fitness of the sirtuin/NAD system is also dependent on co-ordinated regulation of a molecular network of genes that encode seven different sirtuins (SIRT1 – 7) and several biosynthetic enzymes that are required to synthesise NAD. Hence, the intrinsic fitness of the sirtuin/NAD system is very much dependent on genetic factors.

Body stores of NAD are ephemeral, leading to potential nutritional depletion and or insufficiency when requirements for NAD are elevated (e.g. poor nutrition, obesity, diabetes) or demand/consumption pathways are increased (e.g. PARP, CD38 activity).Consequently deficiency should be considered in association with poor nutrition, instances of malabsorption or failure to process bioavailable sources of NAD efficiently and lifestyle factors that increase biological stress (e.g. sedentary behaviour), together with individual genetic factors that dictate the intrinsic fitness of the sirtuin/NAD system. Several strands of sirtuin/NAD research are currently being pursued to define the relationship of the sirtuin/NAD system in glucose and lipid homeostasis, inflammation and oxidative stress and links to health and lifespan.

Research training

The lab has extensive experience working with in vitro, ex vivo and in vivo model systems in addition to human interventions. The student would receive training in experimental design and analysis of different cell and tissue samples to assess regulation of the sirtuin/NAD system. RNA analysis (custom design and application of multiplex PCR assays using GenomeLab technology), molecular biology, biochemistry, immunohistochemistry, proteomics and handling large and complex data sets.