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
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.
Quantitiative Assessment Of Solar UV Exposure For Vitamin D Synthesis In Australian Adults
Funder
National Health and Medical Research Council
Funding Amount
$1,162,536.00
Summary
This research program will add significantly to our current scientific understanding of the dual health outcomes of UV exposure (Vitamin D and skin cancer) . This project is in line with Australia's R and D Priorities, in that it will result in direct and indirect social and economic benefits to Australia by applying the scientific knowledge gained through this research to develop public health initiatives to improve some of Australia's most significant and costly health problems.
The Effect Of High-dose Vitamin-D Supplementation On Mental Health In A Randomised, Controlled Trial Of 1500 Older Women
Funder
National Health and Medical Research Council
Funding Amount
$81,965.00
Summary
Vitamin D is commonly deficient in Western populations, more so in the winter months and in the elderly. A link between depression and vitamin D insufficiency may exist. This study aims to see if vitamin-D supplementation is a practical health intervention for depressive symptoms and may define a public health strategy. In this study participants receive a dose of vitamin D3 or placebo annually for three years. Self-rated psychiatric assessments are administered.
Physiological Function Of The Novel Vitamin D Receptor Isoform
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Vitamin D regulates a wide range of physiological systems including those involved in control of calcium blood level and bone health as well as regulation of the immune system and of cell growth. Vitamin D action is mediated through the vitamin D receptor (VDR), a member of a large family of proteins that regulate the activity of specific target genes that control numerous biological functions. A novel, larger form of the human VDR has recently been described in our laboratory. This novel form s ....Vitamin D regulates a wide range of physiological systems including those involved in control of calcium blood level and bone health as well as regulation of the immune system and of cell growth. Vitamin D action is mediated through the vitamin D receptor (VDR), a member of a large family of proteins that regulate the activity of specific target genes that control numerous biological functions. A novel, larger form of the human VDR has recently been described in our laboratory. This novel form shows differences in activity from the shorter VDR form (VDRA) and also has an unusual distribution within the nucleus of the cell that may relate to its function. The present project focuses on further analysis of the relevance of this novel VDR isoform to normal physiology. We hypothesise that the larger VDR isoform has unique characteristics that may modify how vitamin D works in different cells and tissues, on specific target genes and in response to different active forms of vitamin D. These differences depend on this novel isoform s interaction with specific nuclear proteins that regulate the actions of other hormone receptors. The specific aims of this project are to study the functions of the novel VDR isoform in comparison to VDRA: * On different target genes that are either activated or inhibited in response to vitamin D, and on different cell lines from tissues where vitamin D has important roles, like intestine, kidney and bone * In their response to natural and synthetic vitamin D compounds, because of their possible therapeutic applications * In their interactions with intranuclear regulatory proteins, to understand the underlying mechanisms The study of these two forms of the VDR will help to clarify their potentially different cellular roles and their contribution to the wide range of physiological processes regulated by the vitamin D endocrine system. This understanding may open new paths for treatments of human bone and calcium-related diseases.Read moreRead less
Neonatal Vitamin D Status And Risk Of Schizophrenia: A Replication In Two Independent Samples
Funder
National Health and Medical Research Council
Funding Amount
$346,399.00
Summary
Our group have discovered that low vitamin D (the sunshine hormone) during early life alters brain development. Recently we completed the first study to examine vitamin D in stored blood samples from new born babies and examined their risk of later schizophrenia. This study, based on Danish samples, confirmed a significant relationship between vitamin D levels and risk of later schizophrenia. The current study will examine new samples from Denmark and Scotland in order to replicate this associat ....Our group have discovered that low vitamin D (the sunshine hormone) during early life alters brain development. Recently we completed the first study to examine vitamin D in stored blood samples from new born babies and examined their risk of later schizophrenia. This study, based on Danish samples, confirmed a significant relationship between vitamin D levels and risk of later schizophrenia. The current study will examine new samples from Denmark and Scotland in order to replicate this association.Read moreRead less