© Ageing And Alzheimers Institute 2017 The major focus of research into the Biology of Ageing is on age-related structural changes in the liver. By determining how the liver changes as humans age can result in a better understanding of drug metabolism and improve the treatment of diseases such as Atherosclerosis (the build up of fatty material along the walls of arteries) Vascular disease, Stroke and Parkinson's. The principal roles of the liver include removing toxins from the body, processing food nutrients and helping to regulate body metabolism. While a range of conditions can prevent the liver from performing its vital functions there are also important structural changes that occur as the liver ages. For example, the colour of the liver changes from lighter to darker brown, its size and blood flow decrease and the ability of the liver to metabolize many substances decreases with ageing. Research work on the liver is headed by Professor David Le Couteur AO and has led to the discovery that with advancing age the number of endothelial fenestrae decreases, a process they have called defenestration, with the result that the liver sinusoids become more like vascular blood vessels. It is hypothesised that this process results in the altered exchange of substances between the blood and liver. Recent work has focused on isolating liver endothelial cells and developing techniques aimed at providing more accurate measurements of fenestrae dimensions. The research group is also investigating the  mechanisms of defenestration and the immunology of the liver. The Ageing Liver Diet has a profound effect on ageing. The ageing process can be markedly delayed by caloric restriction and by altering the ratio of protein to other dietary constituents. These effects are in part mediated by a cellular switch called sirtuins that can act as regulatory factors that mediate the life-extending effects of a low-calorie diet. Sirtuins are any of several enzymes that can act as regulatory factors that mediate the life-extending effects of a low-calorie diet. One of the chemicals, a natural substance known as resveratrol, is found in red wines.  Researchers are studying blood samples to determine whether changes in sirtuins are associated with frailty, ageing and death. Part of this work is being conducted in collaboration with the National Institute on Aging in the USA. Ageing Biology, Diet and Sirtuins Link to the Abstract (or full text via suscription) for this article on the PubMed web site. For full details about this research project and contact details link, to the appropriate page at  Centre for Education and Research on Ageing More Details You are here:  > Funded Research > The Biology of Ageing Note: This simplified diagram shows age- related reduction in porosity of hepatic sinusoidal endothelium (pseudocapillarisation) with development of atherosclerosis. Source: Hepatic pseudocapillarisation and atherosclerosis in ageing, David G Le Couteur, Robin Fraser, Victoria C Cogger, and Allan J McLean. The Lancet, Volume 359, Issue 9317, 4 May 2002, Pages 1612-1615 The Biology of Ageing