The Shiels Lab
The Shiels Lab
The Shiels lab has a broad portfolio of Geroscience research interests, meeting at the cross-roads of age related health, the exposome ( i.e. the sum of all environmental exposures across the life course) and the underpinning biology of ageing. The lab seeks to understand the (epi)genetic, molecular and cellular mechanisms that link the exposome to chronic age related diseases of older people. It investigates the interplay between the (epi)genome and both biotic and abiotic factors, such as socio-economic position, nutrition, lifestyle and the environment, all of which can influence individual trajectories of ageing and health.
Current research involves:
- Investigating the role of the microbiota in age related health
- Senotherapies
We have demonstrated that Imbalanced nutrition is associated with accelerated ageing in the general population, mediated by microbiota. We have demonstrated that the most biologically aged in the population exhibit a significantly higher abundance of circulatory pathogenic bacteria, while those less biologically aged possess more circulatory salutogenic bacteria with a capacity to metabolise and produce cytoprotective Nrf2 agonists. We have also shown that those at lower socioeconomic position possess significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group.
We have also undertaken an investigation of CKD and Cancer to establish if the underpinning dysregulated ageing is associated with similar microbial dysbiosis.
For CKD we have now demonstrated that microbial metabolites can contribute significantly to inflammageing and that this can be mitigated by nutritional intervention.
The group is also investigating a range of novel senotherapies designed to combat physiological decline in ageing. These include small molecular analogues to combat inflammageing, naturally occurring senolytics and ncRNA based senolytics.
- Biomimetics
To tackle the ‘diseasome of ageing’ the lab is part of a number of international cross- disciplinary consortia developing a natural sciences approach, based on biomimetics and a re-envisioning of the Hippocratic concept of ‘food as a medicine’, to promote improved health span. Critically, this involves studying non laboratory animal models to see how nature -over millions of years of evolution – has solved health problems that can be found also in humans.