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B J Merry

Publications and source records attributed to B J Merry.

At least 19 recordsLinked to original sources

The influence of age and chronic restricted feeding on protein synthesis in the small intestine of the rat.

Rates of protein synthesis (measured in vivo) and growth of the small intestine were studied as a function of age in ad libitum fed (control) and chronic dietary-restricted rats. At weaning, the fractional rates of synthesis in the mucosal and muscularis externa and serosal layers of the small intestine of control animals were similarly high (90-100% per day). Although these rates subsequently declined with age in the muscularis externa and serosa, they remained constant in the mucosa. Restricted feeding (50% reduced intake), when imposed from weaning onwards, significantly extends the maximum life span of rodents. However, the change in nutritional status slows the accumulation of protein, RNA, and DNA in both layers of the small intestine. Although underfeeding did not prevent the age-related fall in muscularis externa and serosal protein synthesis, significantly higher rates (both fractional and per ribosome) were found when compared age for age with controls. Mucosal fractional synthetic rates were similarly increased by the reduced food intake. These changes in protein turnover in the small intestine are consistent with the higher rates of whole body turnover previously observed in chronically underfed rats.

Aging

Lymphoproliferative responses in diet-restricted and aging Sprague-Dawley rats.

Immunological effects of aging and dietary restriction (i.e., chronic underfeeding without malnutrition) were investigated in male CFY Sprague-Dawley rats. From weaning, diet-restricted animals were given the amount of food that maintained their body weights at approximately 50% of age-matched ad libitum controls. Cells from the spleen, Peyer's patches, brachial/axillary lymph nodes, and mesenteric nodes of 12- and 20-month-old rats were tested in vitro against the T-cell mitogens phytohaemagglutinin and concanavalin A, and the B-cell mitogen Salmonella minnesota lipopolysaccharide (with dextran sulphate). No clear boosting effect of dietary restriction nor age-related decline in T- or B-cell response was observed when a standard foetal bovine serum supplement was used. In general however, serum from diet-restricted rats supported better proliferative responses than serum from age-matched controls, suggesting that dietary restriction may promote lymphocyte proliferation by an indirect mechanism. A feature of this study was the variation in phenotype and immune responsiveness among closely related animals. Thus in an outbred population, any beneficial effects of dietary restriction upon immune responses could be outweighed by variation among individuals.

Aging

Failure of dietary restriction to enhance cytolytic and chemiluminescent activity of peritoneal exudate cells from ageing rats.

Investigations into the cytolytic activity of peritoneal macrophages from male Sprague-Dawley rats (activated in vivo with Corynebacterium parvum) utilised SV40-3T3 and L-929 target cells in a 72 h [3H]thymidine release assay. The dietary restricted rats under test were given a measured amount of food from weaning sufficient to maintain their body weights at approximately 50% of age-matched controls fed ad libitum. Cytolytic activity was similar in the two dietary groups at both 13 and 21 months of age, nor were chemiluminescent responses of peritoneal cells to latex or zymosan particles affected by the dietary restriction. No differences were seen in the effectiveness of zymosan particles opsonised with serum pooled from dietary restricted versus control rats in stimulating chemiluminescent responses by standard preparations of peritoneal cells, and concentrations of serum C3 and IgG appeared to be unchanged by the dietary regime.

Aging

Effect of age and restricted feeding on polypeptide chain assembly kinetics in liver protein synthesis in vivo.

Polypeptide assembly rates during in vivo hepatic protein synthesis were studied as a function of age and restricted feeding in male rats. With ageing the time to assemble the average peptide in the liver of fully-fed rats significantly increased. In young rats maintained on a restricted feeding regime known to retard ageing, the time to assemble the average polypeptide was increased 2.5 times. With ageing the rate of peptide elongation increased so that at 2 years of age the underfed animals assembled peptides at a significantly faster rate than their age-matched controls. The rate of elongation of peptides during hepatic protein synthesis was shown to be directly dependent upon circulating T3 levels rather than the dietary status of the animal. On refeeding young diet restricted rats, polypeptide assembly kinetics did not immediately return to control values although the rate of protein synthesis was significantly increased. Total liver RNA content increased significantly in refed animals allowing for a greater rate of chain initiation to offset the slow rate of chain elongation. A period of 28 days of ad libitum feeding was required before assembly kinetics returned to control values and is probably indicative of a persistent impaired monodeiodination of T4 to T3.

Aging

The effects of age and chronic restricted feeding on protein synthesis and growth of the large intestine of the rat.

1. In vivo rates of protein synthesis and growth of the large intestine were studied in ad libitum fed control and chronic diet restricted rats between 3 and 149 weeks post partum. 2. Restricted feeding (50% reduced intake) when imposed from weaning significantly extends the life span of rodents through an unknown biochemical mechanism. 3. The change in nutritional status slows the accumulation of RNA, DNA and protein in the large intestine but does not modify the fractional rate of protein synthesis. 4. It was therefore deduced, that intracellular protein degradation, or the rate of mucosal cell extrusion into the gut lumen, is accelerated by chronic restricted feeding.

Age Factors

Failure of dietary restriction to influence natural killer activity in old rats.

Natural killer activity of Sprague-Dawley rats maintained on an ad libitum versus restricted diet was compared using an 18 hour 51Cr-release assay, against the K562 erythroleukemic line, Yac-1 lymphoma cells and SV40-3T3 cells. The results indicated that no enhancement of natural killer function was induced by dietary restriction of 10.5-month-old rats from weaning. Prolongation of the restricted diet into late life (24 months) similarly did not enhance basal natural killer activity over levels observed in the ad libitum controls. This suggests that the improved resistance to some tumours seen after prolonged dietary restriction depends on another defensive mechanism, reduced metabolic activity and/or a reduction of available nutrients at cancerous foci.

Age Factors

The effects of aging on carbonic anhydrase concentrations in rat liver and skeletal muscle.

The isoenzymes carbonic anhydrase II (CAII) and III (CAIII) have been measured by radioimmunoassay in the livers of male and female rats aged from 21 to 800 days. No sexual dimorphism at 21 days was found, but from 50 to 400 days both isoenzymes show sexual differences. From 600 days onwards, these differences are less apparent. CAIII concentrations in two 'fast' fibre muscles and one 'slow' fibre muscle have been determined. There is no sexual dimorphism in muscle, but a wide variation between individuals was observed. Fast muscles show maximal CAIII levels at 800 days, whereas in slow muscle the concentration of the isoenzyme is declining at this time.

Aging

Changes in protein turnover and growth of the rat lung in response to ageing and long-term dietary restriction.

The wet weight, protein, RNA and DNA contents of the lung were studied during normal ageing and chronic dietary restriction. The rate of normal lung growth gradually decreased between weaning and old age (105 weeks). However, unlike many other body tissues, there was little or no post-natal decline in the fractional rates of protein synthesis and breakdown. Dietary intervention severely retarded lung growth, particularly at the earliest stage (i.e. 4 weeks), studied. Here the suppression of protein synthesis was due to the combined effects of piece-meal feeding and the long-term effects of the reduced food supply.

Aging

Effects of ageing and chronic dietary restriction on the morphology of fast and slow muscles of the rat.

The soleus and extensor digitorum longus muscles of the hindlimb and the flexor digitorum profundus muscle of the forelimb were studied in ad libitum-fed control and age-matched diet-restricted male rats at various ages from weaning to senescence. Growth of individual muscles was accomplished by fibre hypertrophy and not hyperplasia. Between weaning and one year, fibre numbers remained constant in the soleus but fell by 50% in the extensor digitorum longus. Both muscles displayed increasingly oxidative fibre type profiles with advancing age, irrespective of dietary status. This was particularly noticeable in the soleus, which transformed its fibre population from one containing 35% fast fibres at weaning to one with no fast fibres at 91 weeks. In senility, however, the fibre type population again displayed 25% fast fibres. The capillary: fibre ratio and the capillary density were correlated with muscle fibre size in both hindlimb muscles. Although capillarity increased with age, expected differences between fast and slow muscles were probably minimised by the high proportion of FOG fibres in the extensor digitorum longus. Both hindlimb muscles displayed significant increases in the ratio of connective: muscle tissue with increasing age. The soleus invariably contained more connective tissue than the extensor digitorum longus. Dietary restriction reduced the rate of increase, so that the connective tissue content was approximately one half that found in control muscles at one year. Various pathological features associated with old age were delayed considerably in the muscles of the diet-restricted rats. It is concluded that chronic dietary restriction imposed directly after weaning has a dramatic effect on the normal growth and ageing of skeletal muscle.

Aging

The effects of ageing and chronic dietary restriction on in vivo hepatic protein synthesis in the rat.

Hepatic growth and protein synthesis in vivo was studied with age in ad libitum-fed and dietary restricted rats in which the mean and maximum lifespan was significantly extended. Livers from underfed rats showed significantly lower DNA, RNA and protein contents, and total protein synthesis. The fractional rate of synthesis although initially depressed by restricted feeding, showed no consistent trend with age when compared with control values. The lower fractional rate of synthesis observed in livers from dietary restricted rats at 7 weeks of age is attributable to a significant decrease in ribosomal capacity, with no effect on ribosomal activity being evident. Liver tissue from rats fed ad libitum demonstrated a progressive loss of translational efficiency with age which was delayed by chronic dietary restriction.

Aging

The influence of chronic dietary intervention on protein turnover and growth of the diaphragm and extensor digitorum longus muscles of the rat.

Changes in weight, protein, RNA and DNA contents of the E.D.L. and diaphragm muscles were studied in conjunction with aging and chronic dietary restriction. Between weaning and senescence both muscles exhibited progressive decreases in their fractional rates of growth, protein synthesis and protein breakdown; these rates being age for age higher in the diaphragm. Dietary restriction (50% of ad libitum food intake) from weaning onwards retarded muscle growth, particularly at the early stages (i.e. 4 weeks) after its implementation. Here the suppression of protein synthesis was due to the combined effects of piece meal feeding and long term reductions in food intake. Later, muscle sizes and total, but not fractional, synthetic rates were consistently decreased by chronic dietary intervention. The onset of the ageing atrophy may also be delayed by underfeeding. The changes in these 2 muscles have been compared to those in the whole animal and other striated muscles, as previously reported by the authors.

Animals

Biological mechanisms of ageing.

In a short review of the theories or proposed biological mechanisms of ageing it is necessary to be very selective in the ideas which are included or rejected. Although many theories of ageing are advanced in the literature a high proportion can be considered to be special cases of a previous hypothesis. No one individual theory satisfactorily explains the biological mechanism of ageing, indeed elements of many theories may be required to understand such a complex phenomena. Such a view has been formally expressed by Wright and Davison who consider that all theories represent too simplistic an approach to the understanding of ageing, a biochemical complexity which can only be resolved using system analysis techniques.

Aging

Vasoactive intestinal polypeptide and dopamine in the hypothalamus and pituitary of ageing rats with prolactinomas.

Vasoactive intestinal peptide (VIP), an dopamine have been measured in the hypothalamus and anterior pituitaries of female rats at three different ages. Rats aged 19 months had a high incidence (35%) of prolactin-secreting tumours of the pituitary and these animals had increased hypothalamic and pituitary VIP compared with three-month-old rats or rats without tumours. VIP in old animals without tumours was similar to that in young animals. The third group, with an even more advanced age of 22-28 months, had a lower incidence of PRL-secreting tumours, and pituitary and hypothalamic VIP concentrations similar to those in young animals. Dopamine was significantly increased in the pituitaries of 22-28-month-old nontumorous rats and slightly raised in 19-month-old rats. We conclude that the increased pituitary and hypothalamic VIP content of 19-month-old rats could be a factor in the development of tumours seen at this age, and the differences seen in the two groups of old rats may be related to changes in the steroid environment.

Age Factors

The effect of chronic and acute dietary restriction on the growth and protein turnover of fast and slow types of rat skeletal muscle.

Changes in the growth and protein turnover of the anterior tibialis and soleus muscles were studied in response to acute and chronic dietary restriction (50% of ad libitum intake) between 3 and 149 weeks post partum. The effect of long-term dietary restriction from weaning to senescence was to retard the growth and normal developmental of the two types of skeletal muscle. This was evident from measurements of various parameters of growth, i.e. total protein, RNA and DNA and protein/DNA-P, which were reduced by approximately 50% when compared with age-matched controls. These decreases, however, were not accompanied by a decline in the fractional rate of synthesis (%/day) or ribosomal activity (mg protein/day per mg RNAP). The slowing down of the age-related decline in muscle growth has been attributed to a reduction in RNA capacity (RNA/protein), with similar responses in the fast- and slow-twitch skeletal muscles. The initial effects of piecemeal feeding of this restricted diet on the two types of muscle were also monitored. Short term starvation effects, i.e. 24 hr after feeding a reduced ration, were measured on the protein content and RNA/protein of both the anterior tibialis and soleus muscles; both parameters were unchanged within 24 hr. In contrast, a rapid and significant decline in the ribosomal synthetic activity (mg/d per mg RNAP), and a corresponding fall in the fractional rate of synthesis, occurred within 24 hr of feeding.

Aging

Effects of aging and long term dietary intervention on protein turnover and growth of ventricular muscle in the rat heart.

The developmental growth of the combined right and left ventricles was followed from weaning to senility in rats receiving an unrestricted diet (controls) or pair fed to one half of this food intake. The normal developmental increases in the ventricular weight, protein mass, and nucleic acid contents were retarded by this long term dietary regimen. Although the same maximum values for each variable were ultimately reached in the ventricles of the calorie restricted animals, these were achieved approximately one year later (that is, well into the extended lifespan afforded by such underfeeding). This nutritional slowing of cardiac growth was explained by a retarding of the normal developmental decline in the fractional rates of protein synthesis and protein breakdown (measured in vivo). In the control animals a net loss of ventricular protein occurred over the second year, and this might possibly be associated with a decrease in the mechanical efficiency of the aging heart. Although a similar aging atrophy was found in the ventricles of the diet restricted rats, it was delayed by a year and may be an important factor contributing to the increased longevity. This dietary intervention appears to slow the normal age related changes in cardiac protein turnover.

Aging

Modification of the oestrous cycle hormonal profile by dietary restriction.

In fully fed female CFY Sprague-Dawley rats there was a significant increase in oestrous cycle length with increasing age and a decrease in the percentage of rats with cycles of regular duration. Modification of the rate of reproductive decline could be achieved by restriction of food intake from weaning. Such animals showed retention of regular cycles to a greater age and there was no age-associated change in the length of the oestrous cycle. In dietary restricted females the serum LH peak occurred earlier in the cycle and serum oestradiol-17 beta rose later than in fully fed animals. Both peaks were of reduced amplitude. Serum progesterone values were reduced overall by dietary restriction. Underfeeding resulted in both an increase in serum FSH values and a significant modification of the serum FSH profile.

Aging