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Biomedical subjects

B J Merry

Publications and source records attributed to B J Merry.

At least 37 records · Page 2Linked to original sources

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↗

The control of puberty in the dietary restricted female rat.

Food intake, body weight and serum LH, FSH, progesterone and oestradiol-17 beta were monitored from weaning to puberty in fully fed females housed in groups of four or individually and in females individually housed and dietary restricted. Restriction of food intake from weaning delayed the onset of puberty (34-39 days fully fed, 63-189 days dietary restricted) which was achieved at the same body weight as in the fully fed females. Individual housing of fully fed rats resulted in a significant increase in relative and absolute food intake (but not body weight) and a decrease in serum FSH when compared to group housed fully fed animals. Serum FSH and progesterone were significantly decreased in restricted females and serum oestradiol-17 beta significantly increased.

Animals↗

Lifetime breeding studies in fully fed and dietary restricted female CFY Sprague-Dawley rats. 1. Effect of age, housing conditions and diet on fecundity.

The capacity of female CFY Sprague-Dawley rats to bear multiple litters when breeding was commenced at increasing ages was assessed under the following conditions: continuous housing with male (GC), intermittent breeding of group (GI) and individually housed (I) fully fed animals, restriction of food intake (DR), refeeding of dietary restricted rats (DRA). The percentage of females pregnant, number of litters produced and total litter size were assessed. The number of litters or percent pregnant was unaffected by individual housing but there was a significantly greater decline in total litter size with increasing age of mother when compared to (GI) rats. The slope of the regression line in (I) was identical to that for (GC) females and may reflect the burden of continuous breeding or the stress of individual housing. Both litter size and overall fertility were decreased by dietary restriction but these females did retain their capacity to breed as late as 937 days in contrast to 720 days for any group of fully fed animals. There was no decline in litter size with increasing age in (DR). Returning (DR) rats to full feeding resulted in a rate of decline in litter size identical to that for (GI). All groups of (DRA) produced a maximum of three litters, commencement of breeding at 750 days resulting in production of a litter as late as 952 days.

Aging↗

In vivo DNA synthesis in the dietary restricted long-lived rat.

Male CFY Sprague-Dawley rats maintained at 50% growth rate of ad libitum fed, age-matched control animals showed a 42% extension in maximum lifespan and an increase in the overall doubling time of the rate of mortality from 102 days to 203 days. The slower growth rate of animals on the restricted diet was reflected in lower DNA, RNA, and protein content of liver, kidney and heart with age. DNA synthesis in vivo measured by the incorporation of 3H-thymidine was severely inhibited in liver, kidney, heart, and abdominal skin, particularly during the first six months of life. The developmental peak in DNA synthesis observed in liver and kidney of ad libitum fed animals before 100 days of age was completely inhibited. No effect of restricted feeding on DNA synthesis in the small intestine was observed; however, DNA synthesis was higher in thymic tissue from the experimental animals. A decrease in RNA content of liver, kidney, and heart preceded any change in protein or DNA in animals subjected to restricted feeding. The capacity for protein synthesis (RNA/DNA ratio) was decreased by restricted feeding and was associated with a reduced protein/DNA ratio indicative of reduced cell size during the first six months of life. The translational activity per ribosome (protein/RNA ratio) was not disturbed by undernutrition in any of the tissues studied.

Animal Nutritional Physiological Phenomena↗

The effects of aging and chronic dietary restriction on whole body growth and protein turnover in the rat.

Changes in whole body growth, nucleic acids, and protein turnover have been studied in conjunction with ageing and chronic dietary restriction. Normal developmental changes between weaning and senescence included progressive decreases in the fractional rates of growth, protein synthesis, and protein breakdown; the decline in the synthetic rate correlating with decreases in the ribosomal capacity. Dietary intervention was imposed at weaning and involved pair feeding to 50% of the ad libitum food intake. Although this regime slowed whole body growth by retarding the developmental decline in protein turnover, growth was extended into the second and third years of life. The dietary-induced increase in longevity resulting from a retardation of the ageing process(es) appears therefore to be associated with an enhanced turnover of proteins during the major portion of the life span of dietary restricted rats.

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Levels of O6-methylguanine acceptor protein in tissues of rats and their relationship to carcinogenicity and aging.

N-nitroso compounds react with cellular DNA to produce various damaging adducts, one of the more important being O6-alkylguanine. DNA restoration is accomplished by transfer of the alkyl group to a cysteine residue of an acceptor protein. The levels of acceptor activity were compared in several tissues from well-fed and dietary-restricted inbred SD rats 30-1,194 days of age. Striking and consistent differences were found in the levels of acceptor activity in different tissues from both groups; these levels corresponded to their sensitivity to tumorigenesis by alkylating agents. Acceptor activity levels were highest in the liver and somewhat less in the spleen; there were significantly lower levels in brain and kidney. The random loss with time in the integrity of DNA may cause alterations in cellular function or limit cellular proliferation, thus leading to senescence and death. DNA repair processes may alter the rate of accumulation of damage, thereby affecting potential longevity. There were no significant age-associated changes in the ability of cells from either dietary group to remove DNA adducts and there was no evidence of alterations in the acceptor protein with age that would compromise its functional activity.

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