The Nutritional Geometry Of Ageing In A Rodent Model
Funder
National Health and Medical Research Council
Funding Amount
$979,269.00
Summary
A central belief in ageing research is that eating fewer calories prolongs life, and that the source of calories (carbohydrate, fat or protein) is irrelevant. However, a critical assessment indicates that this conclusion is premature. We will use recent techniques in nutrition to define for the first time in mammals the relationship between diet and ageing in a normal and a prematurely ageing strain of mice. The project will provide a novel nutritional approach for promoting healthy ageing.
Mechanisms Of Proteolysis Of Proteins Containing Oxidised Amino Acids
Funder
National Health and Medical Research Council
Funding Amount
$406,320.00
Summary
There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related d ....There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related diseases, such as Alzheimer s disease and other neurological disorders, are also claimed to be associated with deranged protein oxidation, and accumulation of oxidised products. There is clear evidence that certain defensive mechanisms, such as those acting to remove invading organisms and clear wounds, are also associated with an enhanced production of oxidised proteins. Perhaps the most important component of defense against oxidised proteins is their removal by complete breakdown to constituent components, and excretion. Normally, the machinery for breakdown of proteins is in vast excess over the required rate of degradation. However, clearly in these conditions of accumulation of oxidised proteins, this is no longer the case, or no longer suffices. Mechanisms by which oxidised proteins are degraded are poorly understood, and quite controversial. Therefore, the present studies bring to bear a new approach to studying this issue, which has been developed by the applicants. The aim is to reveal mechanisms involved in the breakdown of proteins containing oxidised amino acids, both in cellular systems, and in vivo. Such an understanding may allow us to envisage how to remove oxidised proteins by therapeutic means and therefore interfere with the development of age-related diseases such as Alzheimer s disease and cataract formation and the diseases of the blood vessels associated with attack and stroke.Read moreRead less
A Cognitive And Neuroimaging Study Of Exceptionally Old Individuals: Sydney Centenarian Study
Funder
National Health and Medical Research Council
Funding Amount
$857,197.00
Summary
Australia has an ageing society. Individuals over the age of 95 years are the fastest growing proportion of this population. Many of these individuals retain good cognitive function. The Sydney Centenarian Study will recruit all individuals 95 and over in 7 local government areas in Sydney to assess their brain function to determine which cognitive faculties are more or less affected, and how this relates to changes on brain scans. This will be related to neuropathology.
Immunisation In Under Studied And Special Risk Populations: Closing The Gap In Knowledge Through A Multidisciplinary Approach
Funder
National Health and Medical Research Council
Funding Amount
$2,499,969.00
Summary
Much of the vaccine research which informs national policy is conducted by the pharmaceutical industry or by government. However, there are critical research gaps in special-risk and under-served populations where targeted research is not commercially viable. These include research in the extremes of age, Indigenous Australians, migrants, refugees, immunosuppressed and traveller populations. This CRE will address research gaps in such populations, which have not been addressed elsewhere, using n ....Much of the vaccine research which informs national policy is conducted by the pharmaceutical industry or by government. However, there are critical research gaps in special-risk and under-served populations where targeted research is not commercially viable. These include research in the extremes of age, Indigenous Australians, migrants, refugees, immunosuppressed and traveller populations. This CRE will address research gaps in such populations, which have not been addressed elsewhere, using novel, multidisciplinary methods.Read moreRead less
Exploration Of Exposures Associated With Bedding That Are Risks For Childhood Allergy And Asthma Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$263,500.00
Summary
Asthma prevalence in Australia has doubled in the last 20 years, with 1 in 4 children now affected. House dust mites are probably the single most important allergen associated with asthma. The prevalence of mite allergy is linked to exposure, and such allergy when combined with high exposure, is a potent risk factor for asthma exacerbations. The current international advice for managing mite-allergic asthma, strongly advocates the use of bedding encasings as the best way to reduce exposure. Howe ....Asthma prevalence in Australia has doubled in the last 20 years, with 1 in 4 children now affected. House dust mites are probably the single most important allergen associated with asthma. The prevalence of mite allergy is linked to exposure, and such allergy when combined with high exposure, is a potent risk factor for asthma exacerbations. The current international advice for managing mite-allergic asthma, strongly advocates the use of bedding encasings as the best way to reduce exposure. However, three recent major trials using encasings and a meta-analysis of earlier trials all fail to show a clinical benefit. One of the applicants (ET) recently showed, using expertise in measuring personal exposure, that these encasings, as used, fail to significantly reduce aeroallergen exposure. By contrast, 3 recent Australian studies, involving the applicants, AK, ALP and NG showed that feather bedding compared to synthetic bedding, was strongly protective for asthma - the opposite of public advice. The suggested mechanisms involve reduced exposure to mite allergens, or altered exposure to bacterial endotoxin, but persuasive experimental support is lacking. We also propose a novel hypothesis that feather exposure may induce allergic 'tolerance'. Currently there is a lack of certainty about valid approaches to prevent asthma, and the Global Initiative for Asthma has described the need to understand mechanisms and improve interventions as urgent. This project is an ideal opportunity to combine the expertise of the CIA (ET) in measuring airborne exposures (mite, endotoxin, proteins) with that of the others who have expertise in children's asthma, and who are already involved in two large clinical trails involving different bedding and allergen avoidance. Our measurements of these bedding exposures and their clinical outcomes will provide, for the first time, a quantitative basis to refine public health allergen-based interventions to prevent and manage asthma.Read moreRead less