Biogerontology Laboratory Projects

Aging and the liver sinusoid

Our group was the first to discover that old age is associated with major structural changes in the endothelial cells in the liver, called pseudocapillarization . In addition we have established that ageing is also associated with significant changes in the other two cells of the sinusoid, the Kupffer cell and the hepatic Stellate cell . We have shown that pseudocapillarization is associated with impaired hepatic metabolism of lipoproteins and more recently, medications and insulin . The major focus of our research is to develop therapies to prevent these ageing changes, primarily in order to prevent cardiovascular diseases and insulin resistance caused by the age-related impairment of substrate transfer in the liver . To do this we are investigating the regulation of the liver sinusoidal endothelial cells with the cutting edge technology: structured illumination three dimensional microscopy; lipidomics and; proteomics . Recently we have established that the key mechanism for regulating fenestrations is lipid rafts, and we are undertaking further studies to develop therapies to increase fenestrations via their effect on rafts.

Sirtuins and the biology of ageing

The sirtuin pathway is involved with mediating the beneficial effects of caloric restriction, and possibly other nutritional interventions on the ageing process . With our international collaborators we have shown that an agonist of the sirtuin pathway called resveratrol has significant effects on the morphology of the liver and the liver sinusoid . We have also investigated the relationship between blood factors that stimulate the expression of the sirtuin pathway in humans . Our results suggest that these factors are associated with frailty in older men from the CHAMP study, and possibly mortality as well . Once the entire cohort of CHAMP subjects has been analysed we will be able to determine the relationship between sirtuin expression and a wide range of age-related outcomes

Nutritional influences on ageing

In collaboration with Professor Stephen Simpson, we are studying the effects of nutrition on ageing . Using a complex mathematical tool called the geometric framework developed by Professor Simpson, we can analyse the relationship between nutrition and outcomes such as aging and frailty in a total novel way . This approach has uncovered the importance of protein in the diet on ageing . In addition, we have also commenced an investigation in humans . Using the CHAMP study of older men, we utilizing the geometric framework to investigate the relationship between macronutrients and health outcomes.