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Biomedical subjects

J E Morley

Publications and source records attributed to J E Morley.

At least 19 recordsLinked to original sources
PubMed2006

Lipid peroxidation in brain during aging in the senescence-accelerated mouse (SAM).

Accumulation of toxic amyloid-beta (Abeta)-peptide is suggested to cause oxidative stress in Alzheimer's disease (AD) brain, and decrease the content of polyunsaturated fatty acids (PUFA) in neuronal membrane lipids. The senescence accelerated prone mice (SAMP8) have age-related increases in the level of hippocampal Abeta-peptide, learning and memory deficits, and a shorter lifespan than their controls. The effects of age-related oxidative damage on PUFA content in membrane phospholipids (PL), and alpha-tocopherol concentration were investigated in hippocampus and amygdala of 2-, 4-, 12-, and 18-month-old SAMP8 mice. In comparison to the younger SAMP8 mice, the hippocampus of the 12-month-old mice contained lower proportions of docosahexaenoic acid (DHA) in phosphatidylserine (PS) and phosphatidylinositol (PI), and higher proportions of arachidonic acid (AA) in PS. Their amygdala contained a lower proportion of AA in phosphatidylcholine (PC). In the hippocampus of the oldest age group, the proportions of DHA in PS, and AA in PC and PI were higher than in the younger age groups. At 2 months of age, the amygdala contained a higher concentration of alpha-tocopherol than the hippocampus, but this difference between the two brain regions was lost with aging. The oldest age group contained the highest concentration of alpha-tocopherol, indicating a protection against oxidative damage of PUFA in brain membrane phospholipids.

Age Factors↗
PubMed2006

Diabetes mellitus in older men.

Most persons with diabetes mellitus are over the age of 60 years. Males develop diabetes more commonly than females. Older diabetics tend to have both impaired insulin release as well as insulin resistance. In older persons diabetes mellitus is associated with decreased functional status and cognitive dysfunction. In general, older persons with diabetes are inclined to be underdiagnosed and undertreated. Managing diabetes in older persons requires special considerations because of their differences in pathophysiology of diabetes and strong association with functional, cognitive impairments and comorbidities. The use of strict therapeutic diets is not recommended in older persons. Treatment of hypertension and hyperglycemia can improve outcomes in older persons. The interdisciplinary team approach is important for care of older diabetic persons.

Aged↗
PubMed2005

The relationship of functional status, nutritional assessment, and severity of illness to in-hospital mortality.

BACKGROUND: Prediction of in-hospital mortality may direct hospital resources towards those patients most at risk. A number of single domain risk instruments have been developed, indicating that functional status, nutritional assessment, and severity of illness individually predict in-hospital mortality. The interaction among these predictors is less well described. OBJECTIVE: To determine the relationship of functional status, nutritional assessment, and severity of illness to in-hospital mortality. DESIGN, SETTING, SUBJECTS: Cohort study of 1712 consecutive admissions over a one year period to an Internal Medical Service at a tertiary university teaching hospital. MAIN OUTCOME MEASURES: Death during hospital admission. RESULTS: Dependency in activities of daily living (OR = 3.37, 95% CI 1.78 to 6.37, p = 0.0002) and body mass index less than 20 (OR = 2.38, 95% CI 1.20 to 4.74, p = 0.01) predicted in-hospital mortality after adjusting for nutritional risk assessment, and severity of illness score. CONCLUSIONS: Impairment in functional status and low body mass index produce the best predictors of inhospital mortality, after adjusting for nutritional risk and severity of illness score. Among these factors, functional impairment may be amenable to correction.

Activities of Daily Living↗
PubMed2005

Testosterone, aging and quality of life.

Testosterone levels decline over the lifespan. Many symptoms of hypogonadism are similar to age-related changes in older males. A small number of studies have suggested that some of these symptoms may be reversed by testosterone. Among them, one trial has suggested that decline in bioavailable testosterone may be related to the development of functional decline. Testosterone replacement during rehabilitation may improve functional outcomes and plays an important role in the maintenance of sexual related quality of life. The overall improvement in well-being and/or health-related quality of life in older males needs to be determined with large placebo-controlled trials. This is particularly important in view of the substantial placebo effect on aging symptomatology.

Aged↗
PubMed2005

The hormonal fountains of youth: myth or reality?

There has been a long search for the best approach of ensuring successful aging. The remarkable demographic transformations in this century have not only led to increased medical needs of older people, who often have multiple chronic conditions, decrements in functional ability and age-related disease, but also to the increase of social expenditures, such as pension funds and health insurance to support them. Therefore, it is no wonder that there is now a great endeavor to find a fountain of youth in both society and individuals. In this review each of the hormones that have been suggested to play a role in rejuvenating older persons, ie, the so-called "hormonal fountain of youth" is briefly discussed. Any hope of a fountain of youth to stop people from getting older, however, is a long way off, with science just beginning to understand the complex genetic, physical and hormonal causes of aging. An essential, but still unanswered question, is whether the age-related decline in hormone systems is physiological, perhaps conveying a benefit, or if the changes are pathological, causing harm. Modern research has, however, demonstrated that the concept of a "hormonal fountain of youth" is predominantly mythological.

Aging↗
PubMed2004

Quantitative proteomics analysis of specific protein expression and oxidative modification in aged senescence-accelerated-prone 8 mice brain.

The senescence-accelerated mouse (SAM) is a murine model of accelerated senescence that was established using phenotypic selection. The SAMP series includes nine substrains, each of which exhibits characteristic disorders. SAMP8 is known to exhibit age-dependent learning and memory deficits. In our previous study, we reported that brains from 12-month-old SAMP8 have greater protein oxidation, as well as lipid peroxidation, compared with brains from 4-month-old SAMP8 mice. In order to investigate the relation between age-associated oxidative stress on specific protein oxidation and age-related learning and memory deficits in SAMP8, we used proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. We report here that in 12 month SAMP8 mice brains the expressions of neurofilament triplet L protein, lactate dehydrogenase 2 (LDH-2), heat shock protein 86, and alpha-spectrin are significantly decreased, while the expression of triosephosphate isomerase (TPI) is increased compared with 4-month-old SAMP8 brains. We also report that the specific protein carbonyl levels of LDH-2, dihydropyrimidinase-like protein 2, alpha-spectrin and creatine kinase, are significantly increased in the brain of 12-month-old SAMP8 mice when compared with the 4-month-old SAMP8 brain. These findings are discussed in reference to the effect of specific protein oxidation and changes of expression on potential mechanisms of abnormal alterations in metabolism and neurochemicals, as well as to the learning and memory deficits in aged SAMP8 mice.

Aging↗
PubMed2003

Efflux of human and mouse amyloid beta proteins 1-40 and 1-42 from brain: impairment in a mouse model of Alzheimer's disease.

Brain to blood transport is believed to be a major determinant of the amount of amyloid beta protein (AbetaP) found in brain. Impaired efflux has been suggested as a mechanism by which AbetaP can accumulate in the CNS and so lead to Alzheimer's disease (AD). To date, however, no study of the efflux of the form of AbetaP most relevant to AD, AbetaP1-42, has been conducted, even though a single amino acid substitution in AbetaP can greatly alter efflux. Here, we examined the efflux of AbetaP mouse1-42, mouse1-40, human1-42, and human1-40 in young CD-1, young senesence accelerated mouse (SAM) P8, and aged SAMP8 mice. The SAMP8 mouse with aging spontaneously overproduces AbetaP and develops cognitive impairments reversed by AbetaP-directed antibody or phosphorothioate antisense oligonucleotide. CD-1 mice transported all forms of AbetaP, although mouse1-42 and human1-40 were transported faster than the other forms. There was a decrease in the saturable transport of mouse1-42 in SAMP8 mice regardless of age. Efflux of mouse1-40 and human1-42 was only by a non-saturable mechanism in young SAMP8 mice and their efflux was totally absent in aged SAMP8 mice. These differences in the efflux of the various forms of AbetaP among the three groups of mice supports the hypothesis that impaired efflux is an important factor in the accumulation of AbetaP in the CNS.

Aging↗
PubMed2003

Impaired cognitive function and mental performance in mild dehydration.

Dehydration is a reliable predictor of impaired cognitive status. Objective data, using tests of cortical function, support the deterioration of mental performance in mildly dehydrated younger adults. Dehydration frequently results in delirium as a manifestation of cognitive dysfunction. Although, the occurrence of delirium suggests transient acute global cerebral dysfunction, cognitive impairment may not be completely reversible. Animal studies have identified neuronal mitochondrial damage and glutamate hypertransmission in dehydrated rats. Additional studies have identified an increase in cerebral nicotinamide adenine dinucleotide phosphate-diaphorase activity (nitric oxide synthase, NOS) with dehydration. Available evidence also implicates NOS as a neurotransmitter in long-term potentiation, rendering this a critical enzyme in facilitating learning and memory. With ageing, a reduction of NOS activity has been identified in the cortex and striatum of rats. The reduction of NOs synthase activity that occurs with ageing may blunt the rise that occurs with dehydration, and possibly interfere with memory processing and cognitive function. Dehydration has been shown to be a reliable predictor of increasing frailty, deteriorating mental performance and poor quality of life. Intervention models directed toward improving outcomes in dehydration must incorporate strategies to enhance prompt recognition of cognitive dysfunction.

Aging↗
PubMed2003

Longitudinal study of fasting serum glucose concentrations in healthy elderly. The New Mexico Aging Process Study.

BACKGROUND: The American Diabetes Association s Expert Committee on the Diagnosis and Classification of Diabetes Mellitus has made the recommendation that all individuals over the age of 45 years should be screened for diabetes every 3 years. OBJECTIVE: This study was designed to determine the necessity for screening healthy elderly (> 65 years) this frequently using fasting serum glucose (FSG) determinations. DESIGN: This is a longitudinal study of initially healthy, upper middle class, community-based volunteers, mostly age 65 years and older at entry into the study. Participants were followed longitudinally with annual FSG concentrations and body mass indices (BMI) for periods up to 18 years (mean 12.4 years). RESULTS: Only 4 of 299 individuals with entry FSG < 126 mg/dl (mean + S.D. age at entry 71.6 + 4.8 years) and 6 or more annual visits have subsequently met the Expert Committee criteria for the diagnosis of diabetes (two consecutive FSGs > 126 mg/dl unless under treatment). When one examines the slopes of FSGs plotted over time (years) for each individual, more participants had a negative slope (220) than positive slope (79), i.e., their FSGs tended to decrease with age. None of the 68 individuals entered age > 75 years subsequently developed diabetes or a significantly positive slope. CONCLUSIONS: It does not appear necessary to screen non-obese elders (excluding minorities) age >65 years with a FSG < 100 mg/dl, or those age >75 years every 3 years as recommended.

Aged↗
PubMed2002

The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics.

BACKGROUND: Previous studies reported that administration of first generation alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake. OBJECTIVES: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured. DESIGN: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption. RESULTS: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test. CONCLUSIONS: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.

1-Deoxynojirimycin↗
PubMed2002

Defining 'relative' androgen deficiency in aging men: how should testosterone be measured and what are the relationships between androgen levels and physical, sexual and emotional health?

In men, bioavailable and free testosterone levels decline by about 1.0 and 1.2% per year, respectively, after the age of 40. The definition of clinically relevant androgen deficiency in the aging male remains uncertain. Clinical features common to both aging and androgen deficiency include decreased muscle mass and strength, and increased fatigue, increased fat mass, loss of libido, erectile dysfunction, impaired cognitive function and depression. It is, however, difficult to separate the effect on plasma testosterone of concomitant disease, compared with the effects of a decrease in testosterone levels alone. Testosterone supplementation has been shown to be effective in improving many of the clinical features of androgen deficiency in the older male, and is safe, at least in the short term. The maximum benefit occurs in those men with the lowest testosterone levels.

Adipose Tissue↗
PubMed2002

Treating malnutrition with megestrol acetate: literature review and review of our experience.

Megestrol acetate is a semi-synthetic progestational steroid that was originally used as a therapeutic modality for metastatic breast and endometrial cancers. What was originally considered to be it's most frequent side effect, an increase in appetite and in body weight, has gradually become an established treatment of malnutrition in patients with the acquired immuno-deficiency syndrome or with non-hormone responsive cancers. The use of megestrol acetate in treating malnutrition in older persons, in patients on dialysis and in a number of other situations is currently under investigation. The authors review the evidence available to support the use of megestrol acetate in treating malnutrition in these selected groups, and the problems associated with administering megestrol acetate; they also report on their own experience with megestrol acetate in the geriatric population.

Acquired Immunodeficiency Syndrome↗
PubMed2002

The GAIN (Geriatric Anorexia Nutrition) registry: the impact of appetite and weight on mortality in a long-term care population.

PURPOSE: To investigate nursing home residents at high nutritional risk to determine: 1) which baseline nutrition or health status indicators correlated with subsequent weight gain or appetite improvement; and, 2) whether a continued weight loss correlated with higher mortality. METHODS: At study entry, nutritional, health status, and demographic data were extracted from the nursing home chart or the MDS. Each subject was tracked for 6 months with survival, weight gain of 5%, and appetite improvement the primary outcome measures. RESULTS: During the 6-month study, younger age was the strongest correlate of appetite improvement. The odds of gaining weight were negatively correlated with BMI, age, and feeding dependency. Subjects who were receiving appetite stimulants (orexigenics) at study entry had a 70% greater probability of gaining weight than those who were not. A weight loss during the 6-month period was associated with a nearly two-fold increase in the likelihood of dying (adjusted RR: 1.95, 95% CI 1.43 to 2.66). CONCLUSION: The course of nutritional problems within nursing homes is highly variable. Continued weight loss, however, appears to have ominous implications for mortality. Younger residents who are not dependent on others for feeding assistance, and who receive orexigenics tend to experience weight gain.

Age Factors↗