Mechanisms For Ageing Changes In The Hepatic Sinusoid
Funder
National Health and Medical Research Council
Funding Amount
$413,750.00
Summary
We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes include thickening of the liver sinusoidal endothelium, deposition of basal lamina and collagen, and marked loss of specialized pores within the endothelium called fenestrations. These changes have profound effects on the transfer of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain ....We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes include thickening of the liver sinusoidal endothelium, deposition of basal lamina and collagen, and marked loss of specialized pores within the endothelium called fenestrations. These changes have profound effects on the transfer of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain in part the fact that old age is the major risk factor for many diseases and adverse drug reactions. To further understand the mechanisms for these important ageing liver changes, we are proposing several studies. First, the effects of caloric restriction on the liver blood vessels will be studied because caloric restriction delays the primary ageing process. Second we will study the effects of ageing on F-actin, ATP, caveolin-1 and VEGF because these mechanisms have established roles in regulating the structure and function of the liver blood vessels and in particular their fenestrations. Finally we will determine whether VEGF can reverse the ageing changes in the liver blood vessels and stimulate the formation of new fenestrations within these blood vessels. Our research provides one mechanism for the inexorable association between old age and susceptibility to disease - based on primary ageing changes in the liver. As well as increasing our understanding of the cellular changes for ageing and the basic mechanisms involved in the regulation of the liver endothelial cells and their fenestrations, this proposed research will provide a foundation for the development of therapeutic interventions for the prevention and treatment of some age-related disorders.Read moreRead less
Autocrine Vitamin D Metabolism, Activity And Bone Health
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
This project will provide the detailed understanding of the activities of vitamin D within the bone microenvironment and offers the exciting prospect of elucidating the mechanistic reasons for maintaining an adequate vitamin D status in relation to the prevention of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function.
Vitamin D And Genetic Susceptibility In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Vitamin D3 levels appear to predict clinical status in multiple sclerosis. The reasons for this are unclear, but may be linked to the effect of the Vitamin D Receptor (VDR) on a subset of immune cells. This project aims to identify key genes which are regulated by this receptor, by using specific gene sequencing technologies combined with knowledge of the genes which confer risk of developing MS. This may help to identify the molecular pathways underlying MS and potential treatment strategies.
The Regulation Of Vitamin D-Dependent Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$612,535.00
Summary
This project aims to establish the cellular basis for the importance of vitamin D in bone. This information is necessary to develop public health nutritional recommendations for improving in skeletal health and reducing the incidence of hip factures in the elderly. Furthermore our data have the potential to reveal novel activities of vitamin D that could eventuate as pharmacological targets.
Roles Of Vitamin D In Skeletal Muscle And Satellite Cells
Funder
National Health and Medical Research Council
Funding Amount
$380,891.00
Summary
Vitamin D deficiency leads to muscle pain and weakness that are reversible with vitamin D supplementation. However, precise biological effects of vitamin D in skeletal muscle are unclear. In this fellowship, novel mouse models and innovative techniques will be used to examine vitamin D signalling pathways in whole muscle and muscle stem cells. Ultimately, the therapeutic potential of the vitamin D pathway in treatment of muscle disorders and age-related muscle wasting will be explored.