Biology of Ageing

The Biogerontology Laboratory

The Biogerontology Laboratory was established within the ANZAC Research Institute at Concord in January 2001. It is the biological research arm of the Centre for Education and Research on Ageing. The major focus is on age-related structural changes in the liver and the implications these changes may have for the development of vascular disease and drug metabolism in the elderly.

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Research Summary

Blood travels through the liver through many small vessels termed sinusoids. These sinusoids differ from normal vascular blood vessels in that they are lined by endothelial cells that are highly perforated by small pores (fenestrae) about 50-100 nm in diameter and which are arranged in structures called sieve plates. The endothelial cells of normal blood vessels are not perforated and form tight junctions between cells to prevent leakage of blood components. In the liver, endothelial fenestrae facilitate the exchange of large proteins and small particles, including lipid-rich blood particles (chylomicron-remnants) between the blood and liver cells (hepatocytes). Our group discovered that with advancing age the number of endothelial fenestrae decreases, a process we have termed defenestration, with the result that the liver sinusoids become more like vascular blood vessels. We have 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. We are also investigating the mechanisms of defenestration and the immunology of the liver.

Our Research Program includes:

• Calorie restriction delays age-related defenestration of the liver sinusoidal endothelium
  HA Jamieson, VC Cogger, SN Hilmer, R Cheluvappa, A Everitt, R Fraser, D Abernethy, R de Cabo, DG Le Couteur
  Details here.


• Diabetes accelerates age-related defenestration of the liver sinusoid
  HA Jamieson, VC Cogger, R Cheluvappa, R Fraser, SM Twigg, SV McClennan, R de Cabo, DG Le Couteur
  Details here.


• Immunology of the Liver
  A.Warren, D. Le Couteur, P. Bertolino (Centenary Institute)
  Details here.


• Mechanisms of Age-Related Defenestration
  J O’Reilly, M Muller, D Le Couteur
  Details here.