Uncovering Sex Specific, Epigenetic Biomarkers Of Healthy Ageing For Targeted Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$1,449,800.00
Summary
The aged population accounts for a significant, and increasing, amount of Australia’s health budget. We aim to uncover novel molecular biomarkers that slow the ageing process and maintain good health for longer. We will use innovative DNA and protein analysis to study the molecular ‘clocks’ of young and old populations and to test whether exercise can slow the ageing process. This will underpin the development of evidence-based biomarkers to be used in personalised health interventions.
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
The Haemodynamic Effects Of Cardiac Compression By Large Hiatal Hernia And The Relationship To Exercise Impairment.
Funder
National Health and Medical Research Council
Funding Amount
$117,270.00
Summary
Large hiatal herniae (HH) often cause debilitating exercise intolerance - the mechanism of which is unknown. This project will define the functional and haemodynamic significance of cardiac compression in patients with large HH, providing new insights into the mechanism of exercise impairment in these patients as well as clinical tools for pre-operative selection of patients likely to benefit most from surgical repair.
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
Supplemental Oxygen In Pulmonary Rehabilitation Trial (SuppORT)
Funder
National Health and Medical Research Council
Funding Amount
$693,838.00
Summary
Approximately 50% of people with chronic obstructive pulmonary disease (COPD) who are referred to pulmonary rehabilitation have a reduction in oxygen during exercise. It is unknown whether providing oxygen during exercise training is beneficial in improving exercise capacity and quality of life in these people with COPD. This national multi-centre research will provide evidence to develop guidelines for the use of oxygen during exercise training in COPD.
Insulin Resistance In Peripheral Artery Disease: Clinical Significance And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This project seeks to improve our understanding and treatment of peripheral artery disease – a condition caused by narrowing/blockages in arteries that supply the legs. Peripheral artery disease affects ~15% of adults >40 years and often causes severe, disabling leg pains during walking. Building on recent findings that peripheral artery disease shares some similar characteristics to type 2 diabetes (“insulin resistance”), a common anti-diabetes drug will be trialled as a potential new strate ....This project seeks to improve our understanding and treatment of peripheral artery disease – a condition caused by narrowing/blockages in arteries that supply the legs. Peripheral artery disease affects ~15% of adults >40 years and often causes severe, disabling leg pains during walking. Building on recent findings that peripheral artery disease shares some similar characteristics to type 2 diabetes (“insulin resistance”), a common anti-diabetes drug will be trialled as a potential new strategy to alleviate these leg pains.Read moreRead less
Role Of AMPK Signaling In Metabolic Control During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$566,288.00
Summary
It is well recognized that sedentary life styles are associated with increased incidence of obesity, Type 2 diabetes and atherosclerotic cardiovascular disease. The medical, social and financial costs of these diseases are growing rapidly and represent a major health care challenge. Exercise is beneficial for maintaining health in patients at risk of developing these diseases and for this reason we are interested in understanding how exercise capacity is regulated.
The Role Of Nitric Oxide In The Regulation Of Skeletal Muscle Glucose Uptake During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participa ....When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participate in blood flow, nerve transmission and immune function, appears to be a necessary component for muscle glucose uptake at rest and during exercise. We have shown that blocking muscle NO production substantially reduces leg glucose uptake during exercise. The aim of this project is to verify this finding and to determine the mechanisms underlying this result. One way we intend to do this is to see whether a drug (Viagra) which increases the effects of NO, raises muscle glucose uptake at rest and during exercise. In rats, a drug almost identical to Viagra stimulates muscle glucose uptake. If Viagra is shown to increase glucose uptake this information may provide the initial human data necessary to develop new drugs to lower blood glucose levels in people with diabetes.Read moreRead less
Improving Functional Capacity In Patients With Chronic Lung Disease With High Intensity Respiratory Muscle Training
Funder
National Health and Medical Research Council
Funding Amount
$340,880.00
Summary
Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these gene ....Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these generalised, broad-based programs result in modest improvements in peripheral muscle function, cardiovascular function, functional exercise capacity and quality of life, it is now apparent they have little or no effect on respiratory muscle function, which is also greatly impaired in COPD. The aims of this study are to answer two longstanding questions that are fundamental to rehabilitation programs in patients with COPD (i) does a program of specific respiratory muscle training alone improve whole-body exercise capacity, dyspnoea, and-or quality of life? and (ii) does the addition of a program of specific respiratory muscle training to a standard whole-body exercise rehabilitation program result in improvemed exercise capacity, dyspnoea and-or quality of life to a greater degree than a program of whole-body exercise training alone? The study is of importance to patients with COPD by investigating the mechanisms underlying the improvement in exercise capacity following a rehabilitation program and the role of respiratory muscle training in such a program. By more accurately defining the mechanisms of exercise limitation we may be able to maximise the benefits obtained during a rehabilitation program, including improved work capacity, reduction in the degree of breathlessness and improved quality of life.Read moreRead less
Type 2 diabetes is a health crisis in Australia. In this project, we will investigate the mechanisms whereby high glucose and fat impair pancreatic beta-cell function leading to type 2 diabetes. We will establish how endoplasmic reticulum stress and the protein Id1 are linked with loss of beta-cell gene expression and function. The information gained will further our understanding of the basic mechanisms regulating insulin secretion and provide new therapeutic targets for diabetes treatment.