Group Of Old Animals Research Articles

Respiratory dysfunction in old mice could be related to inflammation and lung fibrosis induced by hyperphosphatemia.

With age, lungs undergo typical changes that lead to a deterioration of respiratory function. Our aim was to assess the role of age-associated hyperphosphatemia in these changes. We used C57BL6 mice to study an ageing model invivo and human lung fibroblasts were treated with a phosphate donor, beta-glycerophosphate (BGP), to explore mechanisms involved. Respiratory function was registered with a double chamber plethysmograph. Lung structure was analysed by different staining, phosphate and cytokines levels by colorimeric kits, expression of fibrosis, inflammation and ET-1 system by western blot or RT-PCR. Old mice showed hyperphosphatemia, along with lung fibrosis, loss of elastin, increased expression of pro-inflammatory cytokines and impaired respiratory function. BGP induced inflammation and fibrosis in fibroblasts through the activation and binding of NFkB to the MCP-1 or FN promoters. BGP increased ECE-1 expression by inducing NFkB binding to the ECE-1 promoter. QNZ, an NFkB inhibitor, blocked these effects. When ECE-1 was inhibited with phosphoramidon, BGP-induced inflammation and fibrosis were significantly reduced, suggesting a role for ET-1 in BGP-mediated effects.ET-1 produced effects similar to those of BGP, which were also dependent on NFkB. To study the pathophysiological relevance of hyperphosphatemia invivo, a low-P diet was administered to a group of old animals, showing an improvement in fibrosis, inflammation and respiratory function compared to old mice on a standard diet. These results suggest that age-related hyperphosphatemia induces inflammation, fibrosis, and impaired respiratory function in old mice; these effects appear to be mediated by ET-1 and NFkB activation.

Age changes in the lipid profile of rats against experimental metabolic syndrome

Background. Metabolic syndrome (MS) is characterized by the development of pathogenetic mechanisms that potentiate abdominal obesity and insulin resistance. Obesity is a stimulator of the synthesis of active components of adipose tissue – adipocytes (AT), which leads to numerous metabolic and hemodynamic disorders. The study of pathophysiological mechanisms based on the basis of morphometric and biochemical parameters of blood pressure, taking into account age and gender aspects, is of great topical importance. Purpose – of the study is to identify differences in the morphological and histological parameters of adipocytes against the background of the development of metabolic syndrome in animals of different ages and sexes. Materials and Methods. To achieve the goal, an experimental study was conducted on 108 white rats of the WAG/G Sto population. Each age group consisted of a control (36) and an experimental series (72), where the animals were divided by sex. The 1st group included young immature 3-month-old rats of the control (1K) and experimental (1A) subgroups. Group 2 consisted of 36 sexually mature rats aged 5–6 months, divided into 2 subgroups: control (2K) and experimental (2A). The third group consisted of 36 old rats aged 18 months, divided into the control 3K (12) subgroup (6 old females and 6 old males), and the experimental subgroup 3A – of 12 females and 12 males. Results. The hypodermic tissue of all experimental groups consists of adipocytes, the size, shape and density of which had age and gender differences. In group 1A of both subgroups, the cells had a round and oval shape and were significantly smaller in size compared to groups 2A and 3A. Adipocytes of rats have morphological changes against the background of experimental modeling of MS in taking into account age and gender aspects. It was established that in the group of old animals, hypertrophic processes prevail in BP, against the background of greatly reduced hyperplastic processes. Analyzing and comparing the size of adipose tissue cells between experimental groups 1A, 2A and 3A, the dependence of the increase in the size of adipocytes, which is related to the age of the animal, was noted. Conclusions. Experimental changes in the integrative indicators of AT of rats in the pathogenesis of MS are related to age and sex. An inversely proportional dependence of the decrease in the resistance of adipocytes as the age of the animal increases was noted. The obtained results can be designated as a biological marker that determines the development of obesity against the background of disorders of the systemic inflammatory response and insulin resistance.

Probability and number of bruises in bovine carcasses according to animal type, handling and transport.

The aim of this study was to evaluate pre-slaughter risk factors on the probability of bruising and the number of bruises in different regions of the bovine carcass. The study evaluated the data from 4061 batches of slaughtered cattle, totalling 199,026 carcasses, from Hereford and Aberdeen Angus animals in crosses with continental European breeds and Zebu cattle. The factors that caused injury were sex, handling conditions (score), vehicle type, vehicle load density (kg/m2), travel time (minutes), travel distance (kilometres), physiological maturity (dentition), animal reactivity (score), and carcass fat (score). The type of vehicle had the greatest influence on the probability of carcass bruising and affected all carcass cuts. More bruising occurred in vehicles with a greater load capacity. A higher chance of bruising was seen in groups of older animals, those with an excitable temperament and, especially, in groups of females. Higher load densities during transport resulted in a greater chance of bruising occurring in all cuts except the hindquarters. Distance and travel time are unstable in the models, but also detrimental, increasing the probability of bruising and the number of bruises in the various cuts. The results of this study suggest that good practices in the welfare, handling and transport of the animals, as well as training the personnel responsible for their handling, should be adopted to minimise the risk of injury at different locations on the carcass.

Cardiac dysfunction in spontaneously hypertensive old rats is associated with a significant decrease of SUR2 expression.

ATP-sensitive potassium (KATP) channels are participants of mechanisms of pathological myocardial remodeling containment. The aim of our work was to find the association of changes in the expression of Kir6.1, Kir6.2, SUR1, and SUR2 subunits of KATP channels with changes in heart function and structure during aging under conditions of the constant increase of vascular pressure. The experiments were carried out on young and old spontaneously hypertensive rats (SHR) and Wistar rats. The expression levels of KATP channels subunits were determined using reverse transcription and quantitative PCR. It is shown that the mRNA expression level of Kir6.1 in young SHR rats is significantly lower (6.3-fold, p = 0.035) than that of young Wistar rats that may be one of the causes of arterial hypertension in SHR. At the same time, mRNA expression of both Kir6.1 and Kir6.2 in old SHR rats was significantly higher (6.8-fold, p = 0.003, and 5.9-fold, p = 0.006, respectively) than in young hypertensive animals. In both groups of old animals, SUR2 expression was significantly reduced compared to young animals, in Wistar rats at 3.87-fold (p = 0.028) and in SHR rats at 48.2-fold (p = 0.033). Changes in SUR1 expression were not significant. Thus, significant changes in the cardiovascular system, including impaired function and structure of the heart in old SHR rats, were associated with a significant decrease in SUR2 expression that may be one of the mechanisms of heart failure decompensation. Therefore, it can be assumed that increased expression of SUR2 may be one of the protective mechanisms against pathological myocardial remodeling.

Photoperiod-induced alterations in biomarkers of oxidative stress and biochemical pathways in rats of different ages: Focus on individual physiological reactivity

ABSTRACT Effects of photoperiodicity caused by both the age and individual physiological reactivity estimated by resistance to hypobaric hypoxia on the levels of lipid peroxidation, protein oxidation (aldehydic and ketonic derivatives), total antioxidant capacity, activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and biochemical parameters of aerobic and anaerobic pathways in hepatic tissue depending on the blood melatonin level were studied. The study was carried out on 96 6- and 21-month-old male rats divided into hypoxia resistance groups (LR, low resistance, HR, high resistance). The analyses were conducted at four photoperiods: winter (January), spring (March), summer (July), and autumn (October). Our results indicate a significant effect of melatonin, i.e. over 80%, revealed by the complete statistical model of the studied biomarkers of oxidative stress and oxygen-dependent parameters of metabolism. The effects of melatonin vary with age and between photoperiods, which in turn was determined by individual physiological reactivity. In terms of the photoperiods, the melatonin content in the group of the adult animals with low resistance to hypoxia decreased from winter to summer. In a group of old animals in comparison with adults, the melatonin content in all the studied photoperiods was much lower as well, regardless of their hypoxia resistance. In the group of old animals with low resistance to hypoxia, the melatonin content decreased throughout the photoperiods as follows: winter, autumn, summer, and spring. As can be concluded, spring is a critical period for old animals, particularly those with low hypoxia resistance. The important role of melatonin in these processes was also confirmed by our correlation analysis between oxidative stress biomarkers, energy-related metabolites, and antioxidant enzymes in the hepatic tissue of rats of different ages, with different resistance to hypoxia, and in different photoperiods. The melatonin concentration in the blood of highly resistant rats was higher than in those with low resistance to hypoxia. Melatonin determines the individual constitutional level of resistance to hypoxia and is responsible for individual enzymatic antioxidative responses, depending on the four photoperiods. Our studies have shown that melatonin levels are related to the redox characteristics of antioxidant defenses against lipid peroxidation and oxidative modification of proteins in old rats with low resistance to hypoxia, compared to a group of highly resistant adults. Finally, the melatonin-related mechanisms of antioxidative protection depend on metabolic processes in hepatic tissue and exhibit photoperiodical variability in adult and old rats.

СРАВНИТЕЛЬНАЯ ХАРАКТЕРИСТИКА ВЛИЯНИЯ НЕКОТОРЫХ ПРОМЫШЛЕННО ЗНАЧИМЫХ ЛЕКАРСТВЕННЫХ ТРАВ НА СЕРДЕЧНО-СОСУДИСТУЮ И ЛИМФАТИЧЕСКУЮ СИСТЕМЫ СТАРЕЮЩЕГО ОРГАНИЗМА

The purpose of this study was to identify the corrective properties of a number of medicinal herbs for age-related changes in the aging body. In an experimental study on 8 groups of old animals, a number of medicinal herbs of the Kazakh flora were studied: Ziziphora Bunge, Almaty hawthorn, St. John's wort, Echinacea purpurea, kopeechnik, badan thick-leaved on the parameters of the cardiovascular and lymphatic systems. All the medicinal herbs tested by us affected the animal body to some extent and, according to the studied indicators, showed a positive effect in the direction of a younger organism. There was an increase in lymph flow, diuresis, weight loss, changes in the indicators of swellability, blood and lymph viscosity, blood pressure and heart rate. The data from the screening study allowed us to further combine them into a phytocomposition for subsequent studies in order to correct changes in the old body.

Cystic echinococcosis: an emerging zoonosis in southern regions of Khyber Pakhtunkhwa, Pakistan

BackgroundCystic echinococcosis (CE) is one of the principal causes of economic loss to the livestock industry because of its morbidity and mortality of food-producing animals and condemnation of important visceral organs. Pakistan being an agricultural country having an extensive livestock sector, is mostly practiced by poor people, which has a fundamental role in the economy. The present study was aimed to conduct a cross-sectional survey and PCR based confirmation of Echinococcus granulosus in sheep, goats, cows, and buffaloes from southern regions (three districts: Lakki Marwat, Bannu, and Karak) of Khyber Pakhtunkhwa, Pakistan. During the study, a total of 2833 animals were examined randomly including; sheep (n = 529), goats (n = 428), cows (n = 1693), and buffaloes (n = 183). Hydatid cysts were collected and examined for the presence of protoscoleces using microscopy. Detection of DNA was performed by using PCR and two mitochondrial genetic markers namely; NAD-1 and COX-1 were amplified.ResultsThe overall prevalence of CE was found to be (9%) among the examined animals. The hydatid cyst infection was highly prevalent in buffaloes (12%), followed by sheep (10%), cows (9%), and goats (5.1%). Cystic echinococcosis was more prevalent (10%; 96/992) in district Lakki Marwat followed by district Bannu (9%; 112/1246) and Karak (7%; 39/595). Female animals were more likely to be infected with CE (11.6%) than male animals (5.3%) (p = 0.001). Similarly, the infection was higher in the older group of animals as compared to younger (p = 0.001). Mostly (52.2%; n = 129) of hydatid cysts were found in the liver, while (64.4%; n = 159) cysts of the infected animals were infertile. PCR based identification confirmed the presence of E. granulosus sensu stricto (s.s) in the study area.ConclusionCystic echinococcosis was found to be highly prevalent in southern regions of Khyber Pakhtunkhwa and could be a potential threat to human health. Moreover, molecular sequencing and phylogenetic analyses should be carried out in future to identify the prevailing genotype (s) of E. granulosus s.s.

Determining the level of iron in organs of old rats

Introduction: Iron is an essential trace element, vital for numerous physiological processes in the organism. The concentration of iron in tissues must be closely regulated, as it is shown that bigger fluctuations in its concentration could lead to metabolic disturbances and tissue damage. Aging is an universal and inevitable process that leads to a series of adverse changes, as well as imbalances in the amount of trace elements, most often of iron. Iron imbalance in the elderly is a widespread problem, so it is necessary to examine the influence of age on the distribution of iron in the body. Aim: The aim of this paper is to examine whether and how aging affects the distribution of iron in certain tissues (heart, kidney, testis, liver, blood) in experimental animals. Material and Methods: We used male Wistar rats in this experiment. Total of twenty animals were divided into two groups: old and young. Both groups consisted of ten animals. After the completion of the experiment, animals were sacrificed under general anesthesia and their tissues were treated in order to determine the iron content in them. Results: We found a statistically significant increase in the amount of iron in the testicular tissue in the group of old animals (p < 0.001), compared to the control group of young mice. Statistically significant increase was also confirmed in the kidney(p < 0.001), and in blood (p < 0.01). The liver and heart tissue demonstrated a tendency towards decreasing amounts of iron. Conclusion: In this experiment, we demonstrated that age causes a highly statistically significant accumulation of iron in tissues of the testis, kidney and blood, while the amount of iron in the liver and the heart tends to decrease. This kind of changes can create potentially harmful effects on these tissues.

Ontogenic development-associated changes in the expression of genes involved in rat bile acid homeostasis

Ontogenic changes in the rat bile acid (BA) pool, measured enzymatically and by GC-MS, and expression of enzymes (5alpha-reductase, 5beta-reductase, and cytochrome P450 enzymes Cyp7a1, Cyp8b1, Cyp27 and Cyp3a11), transporters [bile salt export pump, sodium taurocholate-cotransporting polypeptide, apical sodium-dependent bile acid transporter, and organic solute transporter alpha/beta (Ostalpha/Ostbeta)], and nuclear receptors [fetoprotein transcription factor (Ftf), farnesoid X receptor (Fxr), small heterodimer partner (Shp), and hepatic nuclear factor 4alpha (HNF-4alpha)], determined by quantitative PCR, were investigated. The absolute size of the BA pool increased progressively up to adulthood, whereas the complexity of its composition was high in fetuses, decreased after birth, increased again progressively up to adulthood, and decreased in aged animals. Allo-cholic acid only appeared early in development, in spite of low 5alpha-reductase expression. The relative size of the BA pool, corrected by liver weight, was maintained from 1 week after birth, except at weaning, when a transient peak accompanied by Shp downregulation and Cyp7a1 upregulation was observed. An imposed weaning delay of 1 week had no effect on the time course of the BA pool size but decreased the proportion of chenodeoxycholic and alpha-muricholic acids, whereas the proportion of cholic acid was increased, probably as a result of Cyp8b1 upregulation. In conclusion, changes in the expression of genes involved in BA homeostasis may play a role in physiological adaptations to digestive functions during the rat life span.

Effect of Recombinant Human Growth Hormone Administration on Body Composition and Vascular Function and Structure in Old Male Wistar Rats

The process of ageing affects negatively both cardiovascular system and body composition. On the other hand, the hormones of the somatotrophic axis, growth hormone (GH) and insulin-like growth factor-I (IGF-I), whose production is reduced by age, are involved in the regulation of the cardiovascular system. The aim of this study was to investigate the effect of GH on body composition, vascular function and structure in old male rats. Old (20 months) and adult (4 months) male Wistar rats were used. One group of old animals was treated with GH for 4 weeks. Periepididimary fat weight, Specific Gravity Index (SGI), dose responses to Acetylcholine (ACh), Isoproterenol (Iso), Phenylephrine (Phe) and ACh in the presence of NG-nitro-L: -arginine metylester (L-NAME; ACh + L-NAME), as well as vascular morphology in aortic rings, were studied. Old rats showed increased fat weight and decreased SGI as compared to adult animals. GH increased SGI and tended to reduce fat weight. Old rats showed an impairment in the vasodilator response to ACh and Iso; GH significantly improved the vasodilatation induced by Iso, whereas the response to ACh was not significantly enhanced by GH treatment. There were no significant differences between adult and old rats in the contractile response to Phe, and GH did not show any effect. Contraction induced by ACh + L-NAME was higher in old rats as compared to adults, and treatment with GH significantly reduced this response. Aortic media area was increased in old rats, and GH administration reduced this parameter. In conclusion, GH shows beneficial effects on body composition, as well as on vascular function and morphology in old male rats.

Body composition and vascular effects of growth hormone administration in old female rats

Aging is associated with alterations in cardiovascular system and changes in body composition. The aim of this study was to investigate the effect of GH on body composition, vascular function and structure in old female rats. Old (20 months) and adult (4 months) female Wistar rats were used. One group of old animals was treated with GH (2 mg/kg/day) for four weeks. Periuterine fat weight, specific gravity index (SGI), dose response to Acetylcholine, Isoprenaline, Phenylephrine and Acetylcholine in the presence of l-NAME and vascular morphology in aortic rings, were studied. Old rats showed increased fat weight and decreased SGI ( p<0.05) as compared to adult animals. GH reduced fat weight ( p<0.05) and tended to increase SGI (NS). Old rats showed impaired vasodilatation to Acetylcholine and Isoprenaline ( p<0.05), and GH improved these responses ( p<0.05). Contraction response to Phenylephrine was higher in old than in adults rats ( p<0.05), but GH did not show any effect. Contraction induced by Acetylcholine+ l-NAME was higher in old rats than in adults, and GH tended to reduce this response, although not significantly. Aortic media area was increased in old rats, and GH reduced this parameter ( p<0.05). In conclusion, GH shows beneficial effects on body composition, vascular function and morphology in old female rats.

Superoxide dismutase, catalase and glutathione peroxidase activities in the liver of young and old mice: linear regression and correlation

Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GP) were determined in the liver of 15 young (3–5 months) and 15 old (23–26 months) female CBA mice. Although, the activities of all three enzymes decreased in aging, only the SOD decline was statistically significant ( P<0.01). The pair wise correlation analysis exhibited an almost identical positive correlation between SOD and CAT in the liver of both young and old mice ( r=0.57), whereas the correlative links between the enzymatic pairs of SOD–GP and CAT–GP were increased in aging. Close to zero in the young group ( r=−0.08), the coefficient of correlation between SOD and GP became highly significant in the group of old mice ( r=0.66; P<0.01). When the coefficients of pair wise and partial correlation were compared, practically no differences were found for the young mice, whereas all three partial coefficients were decreased in the group of old animals. Estimation of the linear regression between the enzymatic pairs revealed higher coefficients of regression and lower intercepts in the group of old mice. The results imply stronger correlative links between the antioxidant enzymes in the liver of old mice, compared with the same indices in the liver of young animals.

Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors

The function of the cholinergic system is known to change during normal aging and in pathological conditions such as Alzheimer’s disease. The present study was designed to assess, within the same group of old animals, the behavioral, electrophysiological and neurochemical effects of chronic treatment with agents that increase the function of the cholinergic system through both muscarinic and nicotinic mechanisms. Doses were determined that produced 60% cholinesterase inhibition by donepezil and galantamine for the old rats. This was chosen to be analogous to therapeutic levels achieved for treatment of human Alzheimer’s disease patients with these agents. Because of the well-known age-related changes in spatial memory and hippocampal synaptic plasticity, spatial working memory in the radial eight-arm maze and hippocampal long-term potentiation induction and decay, as well as nicotinic receptor density and affinity, were measured in old rats implanted with minipumps that delivered donepezil, galantamine or saline. There was no effect of drug treatment on baseline synaptic transmission or on the threshold or magnitude of long-term potentiation induction. Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path–granule cell synapse over the saline control animals, as measured during the week following induction. Both drugs also elevated the number of nicotinic receptors within the hippocampus and neocortex. This is the first demonstration of cholinergic modulation of synaptic plasticity over the time-course of days. Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus. Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze. These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer’s disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.

Age-associated changes in the immune system of German shepherd dogs.

In order to look into the ageing of the canine immune system we investigated age-related changes and associated gender-related differences in parameters of innate and acquired immunity in German Shepherd dogs. We obtained the following findings: white blood cell counts, peripheral blood lymphocytes, lymphocyte proliferative activity and interleukin-2 (IL-2) serum concentrations were significantly lower in the group of old animals, whereas the concentrations of gamma-globulins and the functional activity of the complement system were significantly higher in the elderly. Phagocytic and bactericidal activity of polymorphonuclear cells, as well as their 'killing function,' the serum cytokine-like activities of tumour necrosis factor-alpha and the plasma concentrations of immunoglobulin G, as well as of alpha- and beta-globulins, were not significantly affected by age, whereas natural killer-cell activity and the serum cytokine-like activities of IL-1 were significantly higher only in the group of female old animals. With regard to gender-related differences, lymphocyte proliferative activities as well as plasma concentrations of alpha-globulin were significantly higher in the group of female animals, whereas the absolute numbers of segmented neutrophils were significantly lower. Species analogies with regard to ageing as presumed to exist between man and laboratory rodents also seem to be applicable to the dog. The observed age-related changes in the canine immune system are probably among the main causes for the multimorbidity of old age, affecting life expectancy and mortality in the dog and should be recognized and considered by the attending veterinarian.

Some observations on endemic fluorosis in domestic animals in Southern Rajasthan (India).

Chronic fluoride toxicity in the form of osteo-dental fluorosis was observed in cattle, buffaloes, sheep and goats from 21 villages of Banswara, Dungarpur and Udaipur districts of Southern Rajasthan where the mean fluoride concentration in drinking water varied from 1.5 to 4.0 ppm. The prevalence of dental fluorosis in calves (< 1 year age) was greater than that in adult cattle and buffaloes. At a fluoride concentration in the water of 4.0 ppm, 100% of calves, 65.6% of buffaloes and 61.0% of cattle were found to be affected with dental fluorosis to varying degrees. In the older group of buffaloes, their teeth were brownish black instead of creamy yellow as found in calves and cattle. Out of 780 goats and 564 sheep, none revealed evidence of osteo-dental fluorosis. The overall prevalence of skeletal fluorosis was 8.5%, with the highest prevalence of 29.0% in cattle and 37.5% in buffaloes at a fluoride concentration of 3.2 ppm. None of the calves were affected with skeletal fluorosis. Intermittent lameness was observed in the older group of animals (> 7 years age) at 2.8 ppm fluoride or more in the water. None of the fluorotic animals exhibited any apparent evidence of hypothyroidism, stunted growth or low milk production. There was no correlation between gender and the prevalence of fluorosis, but the prevalence and severity of skeletal fluorosis increased with increasing fluoride concentration and age. Possible factors causing variation in fluorosis in the cattle and buffaloes in villages with identical fluoride concentrations are discussed.

Effect of dietary supplementation with zinc sulphate on the aging process: a study using high field intensity MRI and chemical shift imaging

High field intensity magnetic resonance imaging (HF-MRI) has been applied to the in vivo study of age-related processes of organs located in the cervical-thoracic region in mice and to describe the effects of oral zinc supplementation on these processes. Spin-echo (SE) pulse sequence and chemical shift imaging (CSI) techniques have been used. Aging produced a progressive reduction of muscular masses and of thymic area, whereas the HF-MRI appearances of spinal cord and of salivary glands were unchanged. In some aged animals, subcutaneous fat was reduced while visceral fat was well developed. In the group of old animals supplemented with zinc sulphate, muscular masses were more developed than that of the group of untreated old animals. Oral zinc supplementation also produced an enlargement of the adipose tissue and the thymic area showed an increase of about 65% compared with thymic area measured in the group of old animals used as controls. The present study confirms previous data about the effects of Zn supplementation on aging processes and demonstrates that HF-MRI is a powerful technique to study processes of aging, providing information about the effects of drug treatments on these processes.

Diurnal, photoperiodic, and age-related changes in plasma growth hormone levels in the golden hamster.

The golden hamster has been used extensively as an animal model for the study of both circadian and seasonal rhythms, and their regulation by the light-dark (LD) cycle. More recently, this species has been used to examine how the generation and entrainment of circadian rhythms are altered in advanced age. Recent studies in both humans and rodents indicate that age-related changes in the diurnal rhythm of pituitary growth hormone (GH) release may mediate some of the adverse effects of aging on a variety of physiological systems. As a first step in determining whether or not age-related changes in circulating GH levels are associated with changes in the regulation and/or expression of circadian rhythms, the effects of age on both the ultradian and diurnal patterns of plasma GH levels were determined in 3- to 22-month-old male hamsters that were bled every 15 min for a 24-hr period while entrained to an LD 14:10 light cycle. An additional study involving a similar blood collection protocol examined whether or not the length of the day is involved in the regulation of plasma GH levels. Although the frequency of pulsatile GH release did not change with advanced age, both the mean levels of GH per sample and the mean amplitude per pulse of GH were significantly elevated in 3- to 4-month-old animals, compared to animals that were 12-13, 15-16, or 21-22 months of age. In hamsters aged 3-4 and 12-13 months, there was an increase in both mean levels and the mean amplitude per pulse of GH, but not pulse frequency, during the night as compared to daytime values. No such diurnal rhythm was detected in the two groups of older animals. A clear diurnal rhythm in GH levels was also detected in animals maintained in a short-day (LD 6:18) cycle, and the mean levels of GH per sample were greater in hamsters maintained on short compared to long (LD 14:10) days. These results indicate that there are pronounced age-related changes in pituitary GH release in the hamster, and that both the time of day and the length of the day influence the pattern of GH release.

Cardiovascular effects of adenosine and the adenosine A1 Receptor antagonist NPC 205 are altered with age in guinea pigs

AbstractResponsiveness of the cardiovascular system to the effects of vasoactive agents can vary with age. The endogenous metabolite adenosine has negative chronotropic, inotropic, and hypotensive effects. The purpose of this study was to determine if the effects of exogenously administered adenosine and the adenosine A1 receptor antagonist 1,3‐di‐n‐propyl‐8‐(hydroxyphenyl) xanthine (NPC 205) vary with age. The effects of adenosine on mean arterial blood pressure (MABP), heart rate, and cardiac contractility (LV dP/dt) were investigated in two groups of guinea pigs: a young group (3–4 weeks) and an older group (72–75 weeks). In vivo, the older animals were shown to be significantly more sensitive to the negative inotropic, chronotropic, and hypotensive effects of adenosine, whereas the responses to R‐N6‐phenylisopropyladenosine (R‐PIA), a metabolically stable analog of adenosine, were similar in both age groups. In vitro, right atria from young (3–4 weeks) and old (72–75 weeks) guinea pigs exhibited no age‐related differences in the sensitivity to the negative chronotropic effects of adenosine or R‐PIA. Younger animals were more sensitive to the positive inotropic effects of the adenosine A1 receptor antagonist, NPC 205. In addition, basal heart rates were significantly lower in the older group of animals. It may therefore be concluded that there age‐related effects of adenosine. Furthermore, comparison of the effects of adenosine to the effects of the stable analog R‐PIA and the adenosine antagonist NPC 205 suggests that these differences may be due to changes in adenosine metabolism with age. © Wiley‐Liss, Inc.

Intermittent administration of bovine PTH-(1-34) increases serum 1,25-dihydroxyvitamin D concentrations and spinal bone density in senile (23 month) rats.

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine and metabolic effects of life-long food restriction in rats

The effects of chronic (40%) food restriction from 6 weeks of age were studied in 28-month-old male Fischer-344 rats; the results were compared with ad libitum-fed, old and young male rats at 28 and 3 months of age, respectively. Pituitary luteinizing hormone was similar in all old rats and was significantly lower than in young rats. In old ad libitum-fed, but not in food-restricted rats, serum levels of LH, testosterone and T4 were significantly lower than in young rats. Serum levels of T3 did not differ between young and old rats. Type-II 5'-deiodinase activity in brown adipose tissue was similar in both groups of old animals and was significantly depressed as compared with that in young rats. Serum levels of triglycerides were significantly depressed in food-restricted rats, but were significantly increased in ad libitum-fed rats as compared with young rats. Both groups of old rats had significantly elevated serum levels of cholesterol over that in young rats, but the level was significantly lower in food-restricted as compared to ad libitum-fed animals. The results are consistent with the notion that life-long food restriction tends to preserve the activity of many metabolic functions.