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
Successful Ageing In Older Men – Thriving Not Just Surviving In The Health In Men Study
Funder
National Health and Medical Research Council
Funding Amount
$628,810.00
Summary
Despite “Ageing well, ageing productively” being listed as a research priority, we still do not know what factors increase the ability for people to live a healthy old age, particularly as they enter their older years. Studies suggest that factors in late life have quite different effects on both survival and the major causes of illness. This application will use a large group of older men who have already been followed for 15 years to determine what increases the chance of successful ageing.
The Role Of Central Haemodynamics In Type 2 Diabetes Mellitus-related Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$899,704.00
Summary
Type 2 Diabetes Mellitus is associated with stiffening of major blood vessels which may allow the transmission of harmful pressure to the small vessels of the brain. This may in turn be responsible for damage to brain cells and a greater risk of dementia. This study will use state-of-the art techniques to test this theory. If true, it may open opportunities to reduce the risk of brain disease in diabetes by using therapies to reduce arterial stiffening.
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.
There are many unresolved issues regarding nutrition in old age such as the obesity paradox, protein intake requirements, and dietary needs of obese and frail older people. We have developed a nutritional model, the Geometric Framework, which has the capacity to address complex questions about the relationship between nutrition and ageing and have an established cohort of older men that will allow us to investigate multiple factors involved in age-related changes in nutrition and obesity.
IStoppFalls: ICT Based System To Predict & Prevent Falls
Funder
National Health and Medical Research Council
Funding Amount
$579,018.00
Summary
Technology-based solutions have potential to increase effectiveness of individualized quality healthcare while reducing costs and using scarce human resources to maximum effect. Fall prediction and prevention is a research field where technology can be used to facilitate healthy ageing, well-being and independent living. The primary aim of the iStoppFalls project is to develop and evaluate innovative home-based technologies for continuous monitoring and prevention of falls risk in older adults.
Dissecting Associations Of Estradiol And Testosterone With Cardiovascular Outcomes.
Funder
National Health and Medical Research Council
Funding Amount
$435,082.00
Summary
Controversy persists over whether falling testosterone (T) levels in ageing men increase risk of cardiovascular disease (CVD). T is converted by the enzyme aromatase into estradiol (E2). We will assess whether men with abnormal E2 levels are at risk of CVD, more so than men with low T. We will assess whether differences in the aromatase gene which alter E2 levels also influence the risk of CVD. The results will clarify the importance of hormones to CVD and guide new approaches to its treatment.
Investigation Of The Molecular Basis Of Frailty And Development Of Frailty Biomarkers In A Novel Mouse Ageing Model
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Frailty is a state of high vulnerability for adverse health outcomes, and the prevalence of frailty increases with increasing age. There is very little known about why frailty develops, and there is also no widely accepted, efficient method of determining if someone is frail. This project will test blood markers for frailty, that will allow for optimization of treatment for older frail people and use mouse models of frailty to learn more about why frailty develops.
Brain Ageing - Studying Causes And Developing Interventions
Funder
National Health and Medical Research Council
Funding Amount
$481,156.00
Summary
This fellowship will assist in better understanding the complex reasons for serious conditions (dementia, stroke, falls, walking impairment) affecting brain health in ageing individuals, and in developing ways to reduce the risk or impact of these conditions in affected people.