The 'liver sieve' is a term developed to describe the appearance and the role of fenestrations in the liver sinusoidal endothelial cell (LSEC). LSECs are gossamer-thin cells that line the hepatic sinusoid and they are perforated with pores called fenestrations clustered in sieve plates. There is growing evidence that fenestrations act like a permselective ultrafiltration system which is important for the hepatic uptake of many substrates, particularly chylomicron remnant lipoproteins.
View Article and Find Full Text PDFWe aimed to assess the relationship between Drug Burden Index (DBI), a risk assessment tool that measures anticholinergic and sedative medication exposure and cognitive performance, and cognitive impairment in older people. The study population consisted of community-dwelling older men, 70 years or older, living in Sydney, Australia. The Addenbrooke's Cognitive Examination (ACE) and the Trail Making Task (TMT) cognitive tests were performed, and participants were categorized as having intact cognition, mild cognitive impairment, or dementia using clinical diagnostic criteria.
View Article and Find Full Text PDFGeneral practitioners manage complex medicine regimens and multiple comorbidities in older people. While medicine use usually leads to benefits for older people, the process of prescribing medicines is becoming increasingly complex. The quality use of medicines (QUM) is one of the four central objectives of Australia's National Medicines Policy.
View Article and Find Full Text PDFThe disposable soma hypothesis posits a negative correlation between longevity and reproduction, presumably because these aspects of fitness compete for a limited pool of nutrients. However, diet, which varies widely among animals, could affect the availability of key nutrients required for both reproduction and longevity, especially protein. We used a comparative database of mammal life history data to test the hypothesis that carnivores experience less of a negative relationship between reproduction and longevity than herbivores.
View Article and Find Full Text PDFDiabetes mellitus is associated with oxidative injury to the vasculature. Here, the link between oxidative stress and ultrastructural changes in the hepatic microcirculation was investigated as well as the effects of a synthetic antioxidant, tert-butyl bisphenol (tBP). The study focused on the impact of experimental diabetes on liver sinusoidal endothelial cell (LSEC) fenestrations, which are pores in the liver endothelium that facilitate substrate transfer between blood and hepatocytes.
View Article and Find Full Text PDFObjective: To determine the speed at which the Grim Reaper (or Death) walks.
Design: Population based prospective study.
Setting: Older community dwelling men living in Sydney, Australia.
Proc Natl Acad Sci U S A
October 2011
Although most self-reactive T cells are eliminated in the thymus, mechanisms to inactivate or control T cells specific for extrathymic antigens are required and exist in the periphery. By investigating the site in which autoreactive T cells are tolerized, we identify a unique mechanism of peripheral deletion in which naïve autoreactive CD8 T cells are rapidly eliminated in the liver after intrahepatic activation. T cells actively invade hepatocytes, enter endosomal/lysosomal compartments, and are degraded.
View Article and Find Full Text PDFPurpose: Weight loss is associated with bone loss; however, it is unclear whether loss of fat or loss of lean body mass plays the key role in this relationship. The aim of this longitudinal analysis was to clarify the relationship between hip BMD, hip BMC and whole body BMC with changes in fat and lean tissue mass in older men.
Methods: The Concord Health and Aging in Men Project (CHAMP) is a population-based study in Sydney, Australia, involving 1705 men aged 70-97 years.
Background: past research suggests that fall rates in older persons may differ by ethnicity. The aim of this study was to compare the incidence of falls between older male Italian-born immigrants and their Australian-born counterparts.
Methods: this study analysed data from 335 Italian-born and 848 Australian-born men aged 70 years and over participating in the Concord Health and Ageing in Men Project (CHAMP).
Despite remarkable technological advances in genetics and drug screening, the discovery of new pharmacotherapies has slowed and new approaches to drug development are needed. Research into the biology of aging is generating many novel targets for drug development that may delay all age-related diseases and be used long term by the entire population. Drugs that successfully delay the aging process will clearly become "blockbusters.
View Article and Find Full Text PDFCurr Gerontol Geriatr Res
July 2011
Aging is associated with marked changes in the hepatic sinusoid, yet the effect of old age on hepatic stellate cells (HSC) has not been well described. Transmission electron microscopy and immunohistochemistry were used to study the effects of aging on HSC in livers from rats (3-4 mths versus 24-27 mths) and mice (2-3 mths versus 20-22 mths). Desmin-positive HSC doubled in old age in both mice and rats.
View Article and Find Full Text PDFContext: Frailty, a syndrome of multiple morbidity, weakness, and immobility in aging, is an increasingly urgent threat to public health. Single measures of low serum androgen have been associated with frailty in men, but the contributory role of hormonal changes with time is unassessed.
Objective: The objective of the study was to examine, using longitudinal measurements, the relations of serum androgens, estrogens, gonadotropins, and SHBG to the prevalence and progression of frailty in older men.
Serum uric acid (UA) is a strong endogenous antioxidant. Since oxidative stress has been linked to osteoporosis, we examined the association between serum UA levels and bone mineral density (BMD), prevalent vertebral and nonvertebral fractures, and laboratory measures such as calcitropic hormones and bone turnover marker levels. This cross-sectional analysis consisted of 1705 community-dwelling men aged 70 years or over who participated in the baseline part of the Concord Health and Ageing in Men Project (CHAMP), a population-based study of older men in Sydney, Australia.
View Article and Find Full Text PDFWe investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer (14)C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats.
View Article and Find Full Text PDFThe objectives of this study were to determine whether Drug Burden Index (DBI), a measure of individuals' exposure to anticholinergic and sedative drugs, and Beers criteria, an explicit measure of potentially inappropriate drug use, are associated with function in older adults living in low-level care facilities; and to compare DBI with Beers criteria as a predictor of function in older people. The study population consisted of 115 residents living in low-level care facilities in Sydney, Australia. Data on demographics, drugs, and comorbidities were collected.
View Article and Find Full Text PDFPain is highly prevalent in frail older people who often have multiple co-morbidities and multiple medicines. Rational prescribing of analgesics in frail older people is complex due to heterogeneity in drug disposition, comorbid medical conditions, polypharmacy and variability in analgesic response in this population. A critical issue in managing older people with pain is the need for judicious choice of analgesics based on a comprehensive medical and medication history.
View Article and Find Full Text PDFPoloxamer 407 (P407) is a non-ionic detergent that is used widely in pharmaceutical formulations and personal care products. In animals, P407 causes hyperlipidaemia. P407 is taken up by the liver and causes loss of fenestrations in liver sinusoidal endothelial cells (LSEC), which contributes to the pathogenesis of hyperlipidaemia.
View Article and Find Full Text PDFObjectives: To determine the association between loss of muscle strength, mass, and quality and functional limitation and physical disability in older men.
Design: Cross-sectional study of older men participating in the Concord Health and Ageing in Men Project (CHAMP).
Setting: Elderly men living in a defined geographical region in Sydney, Australia.
Werner syndrome is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many features of Werner syndrome, including a pro-oxidant status and a shorter mean life span. Here, we show that resveratrol supplementation improved the hyperglycemia and the insulin resistance phenotype in these Wrn mutant mice.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
February 2011
In the past, it has been assumed that all the biological and medical changes that occur in old age are deleterious. It has therefore been concluded that treatment and prevention of such changes in old age should increase healthspan and delay death. However, accruing epidemiological and clinical trial evidence in older humans suggests that this is not the case.
View Article and Find Full Text PDFObjective: To determine the proportion of older Australian men who meet the Pharmaceutical Benefits Scheme (PBS) criteria for osteoporosis treatment and are receiving effective treatment.
Design And Setting: A population-based, cross-sectional analysis of the baseline phase of the Concord Health and Ageing in Men Project (CHAMP), a large epidemiological study focusing on the health of older men. Data were collected through questionnaires and clinical assessments.
Background: The drug burden index (DBI) is an evidence-based tool that utilizes pharmacologic principles to calculate an individual's total exposure to anticholinergic and sedative medications. Higher DBI has been associated with functional impairment in observational studies of older people.
Objective: To assess the impact of providing information about DBI to general practitioners (GPs) on prescribing for older people.