A collaborative study between researchers at the Centre for Healthy Brain Ageing (CHeBA) and the Mark Wainwright Analytical Centre has developed a world-first, improved method to measure a coenzyme found in all living cells across biological samples, including brain cells and reproductive cells. The new ‘gold standard’ in this field of metabolomics may inform future understanding of the mechanisms of ageing. The findings were published in the journal Metabolomics.
The coenzyme - nicotinamide adenine dinucleotide (NAD+) – has recently been shown to not only be a regulator of metabolism but also involved in numerous biological and pathophysiological processes including cancer, the stress response, inflammation and ageing.
“Recent discoveries have fuelled enthusiasm to examine both NAD+ anabolic pathways and the NAD+ metabolome in several model organisms,” said Dr Nady Braidy who is head of CHeBA’s Molecular Biology group and senior author on the paper.
“These studies have provided renewed insights into the functional roles of NAD+ and its related metabolites and inspired the development of a sensitive, robust, reproducible and rapid method for concurrent quantitative determination of intracellular levels of NAD+ metabolome in certain cells using liquid chromatography coupled to mass spectrometry,” he said.
Previously, key areas of NAD+ research have been to develop strategies to increase levels of NAD+ in the body. However, these and other metabolites are chemically diverse, thus making their concurrent analysis very challenging.
Lead author Sonia Bustamante, from the Mark Wainwright Analytical Centre, said it was anticipated that the new method to quantify the NAD+ metabolome will help standardise NAD+ research across different laboratories. This is also expected to overcome challenges associated with translation of preclinical studies towards clinical practice making the new measure indispensable for targeted analysis.
“To the best of our knowledge, this is the first study to quantify the entire NAD+ metabolome in primary murine oocyte cultures”, said co-author Professor Perminder Sachdev who is Co-Director of CHeBA.
As chronic age-related oxidative stress is known to induce NAD+ depletion, our newly described testing process can be further used to characterise functional effects of changes to the NAD+ metabolome during ageing in several cells including those in ovaries and in the brain.
“Not only will this research be of benefit in increasing our understanding of the mechanisms of ageing and memory, it will likely be highly relevant to improving fertility and cellular function as well,” said Dr Nady Braidy.