Elizma presented at the annual 2017 A5M conference in Melbourne.
Her presentation investigated the role of the gut microbiome and dysbiotic organisms in the dysregulation of human mitochondrial function and signalling, and how this relates to ageing. Dysbiotic organisms such as candida albicans can manipulate host cellular function to suit their own nutritional and environmental needs in order to facilitate growth and survival. When under threat or starved, candida albicans will manipulate mitochondrial function to further increase their virulence and make them more resistant. They do so by upregulating glycolysis and the glyoxylate pathway to obtain fuel sources and cofactors for growth.
This invariably disrupts the ratio between NAD and NADH which has wide reaching implications. Similarly, other bacterial and parasitic organisms can upregulate or inhibit certain mitochondrial enzymes and contribute to overall oxidative stress and inflammation. This disruption in redox molecules, NAD and NADH, affects cellular signalling which perpetuates mitochondrial dysfunction. This also affects signalling processes in other parts of the body such as SIRT protein expression which regulates a number of biological pathways involved in ageing, apoptosis and inflammation.
Combined with reduced levels of antioxidants due to high oxidative stress, this can create bottle necks in electron transfer. This may result in increased levels of highly reactive oxygen species which will contribute to the ageing process and reduce longevity. Cells under threat will respond with a ‘Cell Danger Response’ as described by Robert K. Naviaux in his paper ‘Metabolic Features of the Cell Danger Response’. In conclusion, the gut plays a significant role in the environmental challenges that cells must endure. By understanding and appreciating the effect that dysbiotic organisms can have on cellular/mitochondrial function, the significance of digestion, diet and the use of antibiotics as well as their influences on health and ageing becomes evident.
