Biological Ageing and Epigenetics
The Shiels lab has recognized expertise in the basic science of the biology of ageing and both its clinical and industrial application. The lab seeks to understand determinants of healthy ageing and psychosocial drivers of ageing and disease, which can then be applied to dissect human disease processes with a view to intervention.
Human ageing is a complex and gradual process that is still not well understood at the biological level. Extrapolation of observations made at the cellular level, to that of the level of a tissue/organ /organism/ is not straightforward. Further extrapolation to the level of a population is even more daunting and suitable molecular markers to dissect this are lacking. There is a paucity of validated markers available with which to study ageing processes in the absence of disease. The Shiels lab has been among the first to validate and apply such biomarkers of ageing identified in the laboratory to both clinical populations and epidemiological cohorts. This has provided:
A new clinical pre-transplant test for post-transplant renal allograft function;
A novel biological readout for public health interventions;
A novel translational tool for toxicological screening in humans.
The lab is also part of a number of National (Halcyon and pSOBID) and International consortiums (BoAT) looking at psychological, sociological and biological determinants of ageing, with special reference to what determines healthy ageing. This is particularly relevant to Glasgow, which has an extremely steep socioeconomic gradient with associated mortality and morbidity, unexplained by conventional risk factors for disease. The biological pathways underlying this disparity in health are not well defined. The Shiels lab has demonstrated that accelerated biological age is a feature of many diseases in Glasgow, including cancer and that lower socio-economic status and poor diet can accelerate biological ageing and predispose to early onset of disease. It has also demonstrated associations between elevated circulating IL-6, a key component of the senescence associated secretory phenotype, with biological ageing, but these associations are lost when analyses are adjusted for socioeconomic status and diet. To tease out potential mechanistic links, Dr Shiels has investigated the epigenetic status of these subjects by using their global methylation content as a novel "bio-dosimeter" to measure the impact of socio-economic and lifestyle factors on disease susceptibility and risk. These studies have clearly demonstrated significant global DNA hypomethylation in the most socio-economically deprived Glaswegians. This appears to be established in utero and is associated with biomarkers of cardiovascular disease (CVD) and inflammation, including fibrinogen and IL-6 in adult life, even after adjustment for socio-economic factors. The lab is now investigating the biochemical pathways by which this may manifest as a disparity in health and early onset disease.
Repair of Organ Damage
The Shiels lab research also focuses on why we get degenerative diseases as we get chronologically older, despite the presence of multi-potent adult stem cells, with a potential repair capacity. The group has isolated and investigated a novel adult cell population that we have termed Pathfinder cells (PCs), which act as paracrine repair initiators. PCs have been demonstrated to induce paracrine repair in STZ-induced diabetes, renal ischaemia and cardiac ischaemia in rodents. This research has been successfully patented and licensed. It has resulted in the formation of a spin out company with Harvard University which was successfully developed as a PLC in 2011.