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The Molecular Mechanisms Of Anabolic Androgen Actions In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in musc ....We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in muscle. We will study the growth of mouse muscle cells in culture, and measure their rate of growth when treated with androgens. All cells contain certain factors that control their growth and replication, and we will test whether androgens activate these factors to increase growth. We will also study the effect of androgens on muscle in mice, to investigate complex effects that only occur in real muscle. We will neuter male mice, which causes muscle wasting. Neutered mice will then be treated with androgens or placebo, and we will compare the muscle growth effect of androgen treatment versus placebo. We will measure muscle strength, size, and the number of muscle cells in treated and placebo mice. We will also see if the effects of androgen require a particular protein, the androgen receptor, which acts as a lock-key mechanism in cells, to allow them to respond to androgens. We will make a strain of mouse with a non-functional version of the androgen receptor only in muscle cells. This will determine if the muscle growth effects of androgens occur through a direct action on muscle, or indirectly through acting on other tissues in the body. This information will ultimately allow us to design more targeted androgen therapies for muscle wasting, that act only on muscle.Read moreRead less
Clarifying Molecular Role Of IGF-1:Ea Isoforms In Skeletal Muscle Hypertrophy And Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$394,718.00
Summary
The growth factor IGF-1 is proposed as a therapeutic agent to increase muscle mass and to reduce muscle wasting resulting from denervation, disuse, ageing and dystrophy. Understanding the precise mechanisms of IGF-1 action is essential for the potential therapeutic use of this factor. This research is focused on the molecular role of IGF-1 in healthy muscle and in the conditions of muscle wasting and degeneration.
IGF-1 AS A THERAPEUTIC AGENT: HOW DOES IGF-1 AFFECT OXIDATIVE STRESS IN DYSTROPHIC AND AGED SKELETAL MUSCLE?
Funder
National Health and Medical Research Council
Funding Amount
$545,243.00
Summary
Loss of skeletal muscle mass (wasting) and function occurs in many clinical conditions, including muscular dystrophy, neuromuscular and inflammatory disorders, and also normal ageing. A growth factor (IGF-1) is a promising therapeutic as it increases protein synthesis. Muscle wasting (loss of protein) is also associated with increased oxidative stress. The project will evaluate the impact of IGF-1 on oxidative stress using genetically engineered mouse models of muscular dystrophy and ageing.
Novel Approach And Insights Into Muscle Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$642,401.00
Summary
The successful use of stem cell therapy absolutely requires the longterm intergration of the therapeutic cells into the target tissue. This application will adapt a chemotherapy-based strategy to drive the successful incorporation and growth of healthy muscle stem cells into diseased muscle. This study will both enhance our understanding of muscle stem cells and provide proof-of-principle for a universal approach to the uptake of stem cells by a target tissue.
Establishing STARS As A Therapeutic Target To Reduce Muscle Wasting And Improve Muscle Function
Funder
National Health and Medical Research Council
Funding Amount
$446,189.00
Summary
Muscle wasting occurs rapidly with disuse after injuries occurring at work, during sport, with chronic disease and in road accidents. It is also a consequence of ageing. Muscle wasting and reduced muscle function places considerable financial strain on our health care system. We aim to use gene therapy and pharmacological interventions to increase the levels of a protein called STARS. We hypothesize that STARS will reduce disuse-induced muscle wasting, increase recovery and improve function.
Concord Hormones And Ageing In Men Project (CHAMP)
Funder
National Health and Medical Research Council
Funding Amount
$1,780,887.00
Summary
Throughout life men have poorer health than women, a health difference that extends into old age. In Australia in 2001, life expectancy for a 65 year old man was 20% less than for a 65 year old woman (81.6 years for men and 85.2 years for women). The study proposed here will fill major gaps in knowledge about key health problems in older men. The study will be called CHAMP: Concord Hormones and Ageing in Men Project. As people grow older, health problems that cause loss of independence and reduc ....Throughout life men have poorer health than women, a health difference that extends into old age. In Australia in 2001, life expectancy for a 65 year old man was 20% less than for a 65 year old woman (81.6 years for men and 85.2 years for women). The study proposed here will fill major gaps in knowledge about key health problems in older men. The study will be called CHAMP: Concord Hormones and Ageing in Men Project. As people grow older, health problems that cause loss of independence and reduced quality of life become increasingly important. The term 'geriatric giants' is sometimes used to describe these disabling syndromes: falls and fractures, cognitive impairment and dementia, urinary incontinence, and poor mobility and functional dependence. CHAMP has been designed to investigate the causes of, and inter-relationships between, these geriatric syndromes in men. Reproductive hormones are responsible for the fundamental biological differences between men and women. Underpinning CHAMP is the idea that age-related changes in reproductive hormones play an important role in the development of the geriatric syndromes in older men. There have been numerous studies of oestrogen and health in older women but only limited research on testosterone and other reproductive hormones in older men. CHAMP will be the largest study of the geriatric syndromes in older men ever conducted. The study will inlvolve 2800 men aged 65 years and over recruited from the community around Concord Hospital in Sydney. These men will each spend 3 hours at the study centre, where they will have a comprehensive physical examination and tests for osteoporosis, muscle weakness, dementia and urinary problems, as well as blood tests. This will all be repeated 2 years later.Read moreRead less
Low Dose Aspirin And Age-related Macular Degeneration: Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,043,189.00
Summary
Age-related macular degeneration (AMD) is a major cause of visual impairment in advanced countries, responsible for nearly half of all legal blindness in Australia. Due to increased life expectancy, the number of people with this progressive late onset disease will double by 2025. Aspirin could prevent or delay the onset of AMD in older persons but its bleeding risk also needs to be considered. This project will determine whether treatment with low dose aspirin reduces incidence or progression o ....Age-related macular degeneration (AMD) is a major cause of visual impairment in advanced countries, responsible for nearly half of all legal blindness in Australia. Due to increased life expectancy, the number of people with this progressive late onset disease will double by 2025. Aspirin could prevent or delay the onset of AMD in older persons but its bleeding risk also needs to be considered. This project will determine whether treatment with low dose aspirin reduces incidence or progression of AMD.Read moreRead less
Novel Muscle Therapeutics Through Selective Beta-Adrenoceptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$603,608.00
Summary
Muscle wasting is an urgent and unmet health risk commonly associated with ageing; cancer, muscle diseases, and conditions including cardiovascular and metabolic disorders. Manipulating beta-adrenergic signalling is a therapeutic target for muscle wasting but treatments have so far been limited due to cardiaovascular side effects. Using cutting edge technologies, we will identify treatments that effectively separate beneficial effects on skeletal muscles from unwanted effects on the heart.