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The Anorexia Of Ageing: Gastrointestinal Control Of Appetite And Feeding In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$190,500.00
Summary
On current projections, the proportion of the Australian population over 65 years will double to 25% in the next 25 years. Ageing is associated with a reduction in appetite and food intake, which has been called the anorexia of ageing. After about age 70, on average, this is associated with loss of body weight, mainly of muscle. The physiological anorexia and weight loss of ageing predispose to pathological weight loss and malnutrition, which is associated with increased morbidity and death rate ....On current projections, the proportion of the Australian population over 65 years will double to 25% in the next 25 years. Ageing is associated with a reduction in appetite and food intake, which has been called the anorexia of ageing. After about age 70, on average, this is associated with loss of body weight, mainly of muscle. The physiological anorexia and weight loss of ageing predispose to pathological weight loss and malnutrition, which is associated with increased morbidity and death rates. High rates of under-malnutrition have been reported among older institutionalised people in the USA and Australia, with lesser, but still substantial, numbers of community-dwelling older people also undernourished. We found recently that 43% of 250 older recipients of domiciliary care services living in their homes in Adelaide were either malnourished or at risk of malnutrition, and had significantly worse outcomes than their well-nourished counterparts over the following year, including increased falls and hospitalisations. Little research has been done to identify underlying causes and develop treatments for this problem. Recent studies, including ours, have shown that upper gastrointestinal (GI) factors (stomach mechanics, rate of gastric emptying, GI hormones including ghrelin, cholecystokinin [CCK] and amylin) have important effects on appetite and food intake, and are often affected by ageing in ways that reduce food intake The proposed studies will investigate this upper GI control of appetite and its contribution to the anorexia of ageing. We will investigate the effects of ageing on gastric factors, including ghrelin release, the satiating effects of CCK and amylin, and the appetite stimulating effects of ghrelin. The expected outcome of this project is a greater understanding of the causes of the anorexia of ageing, enabling the logical development of effective prevention and treatment strategies.Read moreRead less
Intestinal Adaptation Following Massive Small Intestinal Resection: Mechanisms And Management
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation follo ....Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation following massive small bowel resection (MSBR) in order to develop new treatments aimed at improving clinical outcome for patients with SBS. Over the past 5 years we have developed a preclinical model for the study of intestinal adaptation in infants using the juvenile pig. Our recent studies in this model have revealed that elemental formula is inferior to whole protein formula suggesting that the current clinical recommendations need urgent re-evaluation. Using the preclinical model in this proposal, we aim to define the mechanisms underlying the adaptive response and evaluate novel therapies aimed at enhancing adaptation following MSBR. Supplementation of enteral feeds with bovine colostrum isolate resulted in normal growth in the preclinical model despite MSBR. In this proposal we plan to advance this observation for the first time to human clinical trials in infants with SBS. Even small gains in enteral tolerance during the early post-operative period may have a significant impact on morbidity and mortality of children with SBS due to parenteral-nutrition related liver disease and gut-related sepsis. This research proposal provides a unique link between studies aimed at providing the scientific basis for understanding the mechanisms of intestinal adaptation using an established preclinical model and translating the results of these studies onto human trials, taking advantage of the clinical expertise available in the management of children with SBS.Read moreRead less
Human ageing is characterised by reduced appetite and food intake, so that average body weight decreases after 70-75 years. This physiological anorexia predisposes to pathological weight loss and malnutrition, worsening of other illnesses, and increased mortality. This project aims to identify causes of this anorexia of ageing, with a view to developing prevention and treatment strategies. We hypothesise that (1) Satiety signals are overactive in the elderly. We will determine whether older peop ....Human ageing is characterised by reduced appetite and food intake, so that average body weight decreases after 70-75 years. This physiological anorexia predisposes to pathological weight loss and malnutrition, worsening of other illnesses, and increased mortality. This project aims to identify causes of this anorexia of ageing, with a view to developing prevention and treatment strategies. We hypothesise that (1) Satiety signals are overactive in the elderly. We will determine whether older people are more sensitive to gastric distension, which reduces appetite and food intake, by measuring perceptions (fullness, hunger, etc), gastric compliance and food intake during intragastric balloon inflation. This will also be done during nutrient infusion into the small intestine, to assess the interaction between gastric and intestinal satiety factors. The contribution of age-related slowing of gastric emptying to the anorexia of ageing will be assessed and the possibility that reduced energy intake worsens the anorexia of ageing will be examined in a nutrient supplementation study. We will have shown that the release of the satiety hormone cholecystokinin (CCK) is greater in older than young adults and that CCK administration causes a greater suppression of food intake in older people, suggesting that increased CCK activity may be a cause of the anorexia of ageing. We will pursue these findings by attempting to increase appetite and food intake in the lderly by administration of a CCK antagonist (blocker). We will also measure the satiating effects of two other probable satiety hormones, amylin and glucagon like peptide 1 in older and young people. (2) The feeding drive is reduced in the elderly Opioids stimulate feeding. In animals this effect is reduced by ageing. To determine whetther this is also so in humans, the suppressive effect of the opioid antagonist naloxone on feeding will be assessed in young and older subjects.Read moreRead less
The Effect Of Exogenous Hormones, Smoking And HPV On The Incidence Of Screen Detected Pre-invasive Cervical Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,201,168.00
Summary
Cervical cancer is one of the leading causes of cancer death in women internationally. About 15,000 women are detected in NSW annually as having pre-invasive cervical cancer (cervical intraepithelial neoplasia (CIN) grade I, II or III). Infection with certain high risk human papillomaviruses is known to be necessary for the development of cervical cancer. In addition, recent long term exposure to smoking and to hormonal contraception are two new factors considered as independent risk factors for ....Cervical cancer is one of the leading causes of cancer death in women internationally. About 15,000 women are detected in NSW annually as having pre-invasive cervical cancer (cervical intraepithelial neoplasia (CIN) grade I, II or III). Infection with certain high risk human papillomaviruses is known to be necessary for the development of cervical cancer. In addition, recent long term exposure to smoking and to hormonal contraception are two new factors considered as independent risk factors for the disease. Hormone replacement therapy (HRT) preparations taken around the menopause are a similar composition to hormonal contraceptives, (oestrogen and progestogen), therefore women on HRT may also be at increased risk. No comprehensive study exists internationally to measure the relative importance of these exogenous hormones on the development of pre-invasive cervical cancer in a way that is of public health relevance (e.g. recent long-term use of oral contraceptives and time since stopped, and among smokers and non-smokers). No Australian data are available on the proportion of women who are current users of hormonal contraceptives or HRT. No local prevalence data on the major high risk HPV subtypes (e.g. 16, 18, 33, 45) are available for Australia to describe its distribution and to inform the cervical screening program and future vaccine initiatives. The NSW Pap Test Register holds the screening history of all women on the cervical screening program, hence this is an ideal source for recruiting a representative sample into a study. We wish to conduct a large study of ~2600 NSW women using the NSW Pap Test Register to measure the relative importance of hormones, smoking and HPV infection on the development of CIN II or III.Read moreRead less
Regulation Of Cellular Responses To Neuropeptides.
Funder
National Health and Medical Research Council
Funding Amount
$83,510.00
Summary
Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction ....Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction in response is termed desensitization is thought to turn off the response to cells following stimulation by neuropeptides. In this study, I will investigate the mechanisms behind the desensitization of VPAC receptors which are a found throughout the body and have many important roles for example, gastrointestinal, pancreatic and reproductive function and control of muscle. VPAC receptors are also highly expressed in certain many cancers such as breast, prostate and colon carcinoma. The wide variety of functions that these receptors perform and the wide distribution in the body suggest that these are very important receptors. To date research into the responses and desensitisation of these receptors has been lacking, and the work that has been done has become confusing as more receptors and neuropeptides which bind them are discovered. The current project aims to carefully study these receptors and to determine their role in health and disease. The understanding the interaction of receptor and neuropeptide can perhaps lead to development of new therapeutic agents.Read moreRead less
Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have b ....Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have been used extremely successfully in the treatment of some leukaemias. Unfortunately, retinoids have not worked as well in other cancers. We have identified an important role for abnormal retinoid function in the evolution of pancreatic cancer, which may be responsible for the lack of effective response to retinoid treatment. This project focuses on identifying if these abnormalities in retinoid function can be reversed with adding specific pharmaceuticals so that retinoid based therapies will be effective in pancreatic cancer.Read moreRead less
Inflammation Drives TFF2 Epigenetic Silencing In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$618,909.00
Summary
Over one million deaths from stomach cancer will occur annually in the next decade. This often fatal disease can be caused by infection from childhood by the bacterium H. pylori. We will study a new link between the inflammation caused by H. pylori and a type of mutation known as epigenetic silencing that switches off a gene which normally prevents stomach cancer. Understanding this process will help us to discover approaches for early detection of stomach cancer and lead to the development of n ....Over one million deaths from stomach cancer will occur annually in the next decade. This often fatal disease can be caused by infection from childhood by the bacterium H. pylori. We will study a new link between the inflammation caused by H. pylori and a type of mutation known as epigenetic silencing that switches off a gene which normally prevents stomach cancer. Understanding this process will help us to discover approaches for early detection of stomach cancer and lead to the development of new drugs that prevent disease.Read moreRead less
LKB1 - The Link Between Obesity And Breast Cancer In Postmenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Obesity is a worldwide epidemic affecting 60% of Australians and is linked to many diseases including breast cancer. Changes in sex hormone levels during menopause may cause these diseases. The focus of this proposal is to determine the role of the sex hormones to regulate a protein (LKB1) involved in both fat metabolism and cancer. This research will benefit the ageing population by making a contribution toward generating therapeutics to combat obesity and breast cancer.