Regulation Of The Beta-secretase (BACE1) By Glycosaminoglycans
Funder
National Health and Medical Research Council
Funding Amount
$561,212.00
Summary
Alzheimer's disease is the leading cause of dementia in the elderly. Because of the prolonged institutionalisation of patients, it is a major health care burden. This project aims to develop novel drugs which can treat Alzheimer's disease by inhibiting production of the protein which causes the neurodegeneration.
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 Receptor-associated Protein (RAP) As A Molecular Chaperone For The Amyloid Protein (Abeta) Of Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$402,403.00
Summary
Our research will examine the role of a protein known as the receptor-associated protein (RAP) in Alzheimer's disease. We will determine whether the protein contributes to the progression of Alzheimer's disease and we will examine the possiblity that that RAP may be used as a drug to treat the disease. The project could potentially have direct benefit for patients by leading to an effective treatment for dementia associated with Alzheimer's disease.
A Population-based Cohort Study Of Brain Ageing - Rates Of Brain Structural Change, Functional Effects, And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$1,323,361.00
Summary
This study will provide unique longitudinal Australian data on the effects and causes of brain aging in a population-based sample of older people. The results may assist in preventing dementia and falls, major public health problems in older Australians.
A Population-based Study Of Cerebrovascular Mechanisms Underyling Gait, Balance And Cognition In Older People
Funder
National Health and Medical Research Council
Funding Amount
$528,330.00
Summary
Mobility problems, falls and dementia are among the major problems affecting older Australians with significant consequent disability. Treatment of such disorders carries an estimated annual cost of around 4 billion dollars. This study will examine the role of age-related brain changes in causing problems with walking, balance and cognitive abilities in the general community. The clarification of the role of the ageing brain in causing such disorders will guide efforts directed at preventing the ....Mobility problems, falls and dementia are among the major problems affecting older Australians with significant consequent disability. Treatment of such disorders carries an estimated annual cost of around 4 billion dollars. This study will examine the role of age-related brain changes in causing problems with walking, balance and cognitive abilities in the general community. The clarification of the role of the ageing brain in causing such disorders will guide efforts directed at preventing the occurrence of falls and dementia.Read moreRead less
Predicting Health And Disease In Australian Men Over The Age Of 80 Years - The Health In Men Study
Funder
National Health and Medical Research Council
Funding Amount
$528,754.00
Summary
Australia is ageing rapidly but we still do not know whether the risk factors, such as health and lifestyle, that predict ill health in middle aged people, apply to people as they reach old age. This study of a large group of older men will examine the type and level of risk factors that apply to men aged beyond 75 years. It will not only determine rates of disability and mortality but also health service outcomes, including hospitalisation, and residential and community care usage.
The Effect Of Hepatic Pseudocapillarisation Of Old Age On The Disposition Of Chylomicron Remnants And Chylomicrons
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
Old age is the major risk factor for atherosclerosis, and vascular disease secondary to atherosclerosis (eg heart attacks and strokes) is the major cause of death and disability in the Western World. As yet there has not been any clear explanation for why old age itself is a risk factor for atherosclerosis. In this study, we are investigating how changes in the liver in old age predispose to hyperlipidaemia and hence vascular disease. We recently discovered changes in the blood vessels of the li ....Old age is the major risk factor for atherosclerosis, and vascular disease secondary to atherosclerosis (eg heart attacks and strokes) is the major cause of death and disability in the Western World. As yet there has not been any clear explanation for why old age itself is a risk factor for atherosclerosis. In this study, we are investigating how changes in the liver in old age predispose to hyperlipidaemia and hence vascular disease. We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes have profound effects on the transport 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. In this study we are interested in the transfer of fats called chylomicron remnants from blood into the liver. Chylomicron remnants are lipoproteins rich in triglycerides that are produced after meals and broken down by the liver. In order to be metabolised, chylomicron remnants must pass through pores in the liver blood vessels called fenestrations. In old age, we have found that these fenestrations are reduced substantially, which will impair the uptake of chylomicron remnants by the liver, leading to marked increases in fat in the blood stream after meals. In this study, we will examine the effects of old age on the ability of the liver to metabolise chylomicron remnants, in particular focussing on the effects of the age-related loss of fenestrations on chylomicron remnant uptake. As well as providing an understanding of the crucial link between ageing and atherosclerosis, the studies will provide a potential new therapeutic target for the prevention of atherosclerosis in older people.Read moreRead less
The ability to monitor one's cognitive performance deteriorates with normal ageing, and is particularly affected in a range of clinical conditions of older age, such as Parkinson's Disease, where it is a predictor of a poor prognostic outcome. This project aims to clarify the effects of age on cognitive and neural processes underlying performance monitoring, as an important first step to improving interventions for age-related impairments, including those accompanying neurodegenerative diseases.
Service Pathways For Ageing Caregivers Of Adults With Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$143,613.00
Summary
Caregiving is demanding, but for most it is but a phase of life. This is not so for the 90,000 Australian parents caring for a lifetime for their adult son or daughter with intellectual disability. They are at significant risk from the physical and emotional consequences of long-term caring and the compounding effects of their own - and their son or daughter's - ageing. Despite this, these ageing parent caregivers typically do not use health and community services until a crisis occurs. Our goal ....Caregiving is demanding, but for most it is but a phase of life. This is not so for the 90,000 Australian parents caring for a lifetime for their adult son or daughter with intellectual disability. They are at significant risk from the physical and emotional consequences of long-term caring and the compounding effects of their own - and their son or daughter's - ageing. Despite this, these ageing parent caregivers typically do not use health and community services until a crisis occurs. Our goal is to ensure that ageing parent caregivers use health and community services appropriately and for these services to be appropriate to their needs. The proposed project therefore aims to identify the pathways that lead to or prevent ageing parent caregivers accessing services and to construct a model for ageing parent caregivers' involvement with services that could be tested with a randomised clinical trial. Narrative life history method will be used to determine how ageing parent caregivers arrived in their present circumstances and factors which influence the caring relationship, its stresses and rewards, and their experiences and views concerning services. Service providers will participate in focus groups to examine their perceptions and expectations of services for ageing parent caregivers. Characteristics of the study sample will be compared with state and national population benchmarks. The findings will inform our planned development of a multi-dimensional strategy to provide cost effective preventive health and community services for this largely neglected subgroup within the population of caregivers in Australia.Read moreRead less