Wistar Rats Of Different Ages Research Articles

Ишемические изменения в головном мозге белых крыс разного возраста после введения инсулина

The morphological changes in the brain tissue of Wistar rats of different ages after intramuscular insulin injection in the dose of 1 IU/kg are typical for the hypoxic lesions of nervous tissue. The brain of rats at the age of 1-2 months responds to increased deposition of glycogen, moderate swelling around the cells and blood vessels. The effect of insulin on the brain Mature rats at the age of 5-7 months leads to vasodilatation, more pronounced swelling around the cells and blood vessels, hypertrophy of cells, aggregation and diabetes of red blood cells. The severity of ischemic changes significantly increased in the brain of old rats at the age of 20-24 months. These old rats had the senile dendrites, the widespread hypertrophic degenerative changes, i.e. flask-shaped vasodilation, hyperemia. In most of the visual fields are detected capillaries with the presence of aggregation on the side erythrocytes, signs of micro thrombosis, hemorrhage areas. The authors note that there is a loss of tone and tortuosity of the small arterioles, widespread swelling around the cells and around the blood vessels. Morphological signs of brain reaction on insulin injection reflect the death of cortical neurons, marked swelling of the brain tissue, disruption of vascular permeability, the thrombus formation and hemorrhages.

Age-related testicular toxicity of mGluR5 negative allosteric modulators appears to be unrelated to testis drug transporter maturity.

Testicular degeneration was observed in exploratory toxicity studies in Wistar rats treated with several mGluR5 negative allosteric modulators. To determine if these testis effects were influenced by animal age, these compounds were administered to male Wistar rats of different ages (8, 10, and 12 weeks old) for 2 weeks followed by evaluation of male reproductive organ weights, testis histopathology, and inhibin B levels. Overall, seminiferous tubule degeneration was observed in 2/15, 5/15, and 0/15 compound treated rats from the 8, 10, and 12 week old cohorts and inhibin B was decreased in 8 and 10 week old animals, but not in 12 week old rats, suggesting that there is an age-related component to this testis toxicity. The gene expression profiles of drug transporters in the testis of rats aged PND 38 through PND 91 were very similar, indicating that immaturity of these transporters is an unlikely factor contributing to the age-related toxicity.

Swimming exercise and diphenyl diselenide-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats

The increase in the inflammatory process is one of the main factors that contribute to aging. The aim of this study was to investigate the effects of a diphenyl diselenide (PhSe)2-supplemented diet (1p.p.m., 4weeks) and swimming exercise (3% of body weight, 20min per day, 4weeks) on the serum levels of cytokines in Wistar rats of different ages. The results demonstrated an increase in the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFα and INFγ) and a decrease in the levels of IL-10, an anti-inflammatory cytokine, with age. In middle-age rats, the swimming exercise and (PhSe)2-supplemented diet decreased serum levels of pro-inflammatory cytokines and increased the levels of IL-10. By contrast, in old rats the swimming exercise protocol increased the serum levels of pro-inflammatory cytokines and decreased the levels IL-10. Diet supplemented with (PhSe)2 did not alter the serum levels of cytokines in old rats. Middle-age and old rats subjected to swimming exercise and supplemented with (PhSe)2 in the diet had a decrease in the serum levels of pro-inflammatory cytokines and an increase in the levels of IL-10. This study demonstrated that swimming exercise and (PhSe)2-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats. (PhSe)2 supplemented in the diet had an anti-inflammatory effect, similar to that of induced by swimming exercise, in middle-age rats and reversed the pro-inflammatory effects of swimming exercise in old rats.

Development of nNOS-positive neurons in the rat sensory and sympathetic ganglia

Neurochemical features in sympathetic and afferent neurons are subject to change during development. Nitric oxide (NO) plays a developmental role in the nervous system. To better understand the neuroplasticity of sympathetic and afferent neurons during postnatal ontogenesis, the distribution of neuronal NO synthase (nNOS) immunoreactivity was studied in the sympathetic para- and prevertebral, nodose ganglion (NG) and Th2 and L4 dorsal root ganglia (DRG) from female Wistar rats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old, 6-month-old, 1-year-old, and 3-year-old).nNOS-positive neurons were revealed in all sensory ganglia but not in sympathetic ones from birth onward. The percentage of nNOS-immunoreactive (IR) neurons increased during first 10days of life from 41.3 to 57.6 in Th2 DRG, from 40.9 to 59.1 in L4 DRG and from 31.6 to 38.5 in NG. The percentage of nNOS-IR neurons did not change in the NG later during development and senescence. However, in Th2 and L4 DRG the proportion of nNOS-IR neurons was high in animals between 10 and 30days of life and decreased up to the second month of life. In 2-month-old rats, the percentage of nNOS-IR neurons was 52.9 in Th2 DRG and 51.3 in L4 DRG. We did not find statistically significant differences in the percentage of nNOS-IR neurons between Th2 and L4 DRG and between young and aged rats.In NG and DRG of 10-day-old and older rats, a high proportion of nNOS-IR neurons binds isolectin B4. In newborn animals, only 41.3%, 45.3% and 28.4% of nNOS neuron profiles bind to IB4 in Th2, L4 DRG and NG, respectively. In 10-day-old and older rats, the number of sensory nNOS-IR neurons binding IB4 reached more than 90% in DRG and more than 80% in NG. Only a small number of nNOS-positive cells showed immunoreactivity to calcitonin gene-related peptide, neurofilament 200, calretinin. The information provided here will also serve as a basis for future studies investigating mechanisms of the development of sensory neurons.

Unique thermal behavior of sphingomyelin species with nonhydroxy and 2-hydroxy very-long-chain (C28-C32) PUFAs

In rat germ cells and spermatozoa, sphingomyelin (SM) contains molecular species with nonhydroxy (n) and 2-hydroxy (h) very-long-chain polyunsaturated fatty acids (V), the most abundant being SMs with (n- and h-) 28:4n-6, 30:5n-6, and 32:5n-6 as acyl chains. The aim of this study was to gain information about their thermotropic behavior and interactions with other lipids. After isolation from rat testis, multilamellar and giant unilamellar vesicles from these SMs were examined using fluorescent probes. Only n-32:5 SM and h-32:5 SM displayed a gel-liquid transition temperature (Tt ∼ 21-22°C), the rest remaining in the liquid state in the 5°C-45°C range. The degree of order was larger in bilayers of any of the h-V SMs than in those of their chain-matched n-V SMs. Both, but n-V SM relatively more than h-V SM, decreased the Tt of dimyristoylphosphatidylcholine as their proportion increased in binary phosphatidylcholine:SM liposomes. In contrast to the established ability of 16:0 SM to form lateral cholesterol/SM-rich ordered domains in ternary dioleoylphosphatidylcholine:cholesterol:SM bilayers, neither n-V SM nor h-V SM showed a tendency to do so. Thus, these SMs are in the fluid state and are not involved in this type of domains in spermatozoa at physiological temperatures. However, this state could be altered at the very low temperatures at which these gametes are usually preserved.

Postnatal fate of the ultimobranchial remnants in the rat thyroid gland

The ultimobranchial follicles (UBFs) are considered embryonic remnants from the ultimobranchial body (UBB). They are follicular structures that vary in size and appearance depending on the age of the rat. The main objective of this article was to study the progressive changes in shape, size, and frequency of the UBFs in the postnatal rat, from birth to old-age. To accomplish that objective, a systematic morphometric and incidental study of the UBF has been carried out in 110 Wistar rats of different ages and both sexes, divided into three groups: 1) young rats (5-90-day-old); 2) adult rats (6-15-month-old), and 3) old rats (18-24-month-old). The glands were serially sectioned and immunostained for calcitonin at five equidistant levels. According to our results, UBFs were observed in all thyroid glands but a more exhaustive sampling was occasionally necessary in male rats. In young rats, immature UBFs predominantly appeared whereas in adult rats, mature UBFs with cystic appearance and variable luminal content prevailed. We frequently found spontaneous anomalous UBFs in old rats, which we have termed as "ultimobranchial cystadenomata." Additionally, in young rats, UBF areas significantly increased with age and they were larger when compared to that of normal thyroid follicles. Likewise, in adult rats, UBFs were significantly larger than normal thyroid follicles but only in female rats. In general, UBFs in females were also significantly larger than those found in male rats. Finally, all these differences related to UBFs together with a higher incidence in females of UB cystadenomata suggest a sexual dimorphism in regard to the destiny of these embryonic remnants during postnatal thyroid development.

Metabolic syndrome markers in wistar rats of different ages.

In recent decades, metabolic syndrome has become a public health problem throughout the world. Longitudinal studies in humans have several limitations due to the invasive nature of certain analyses and the size and randomness of the study populations. Thus, animal models that are able to mimic human physiological responses could aid in investigating metabolic disease. Thus, the present study was designed to analyze metabolic syndrome markers in albino Wistar rats (Rattus norvegicus) of different ages. The following parameters were assessed at two (young), four ( adult), six (adult), and twelve (mature) months of age: glucose tolerance (glucose tolerance test); insulin sensitivity (insulin tolerance test); fasting serum glucose, triglycerides, total cholesterol, HDL cholestero, and LDL cholesterol concentrations; glucose uptake in isolated soleus muscle; and total lipid concentration in subcutaneous, mesenteric, and retroperitoneal adipose tissue. We found that aging triggered signs of metabolic syndrome in Wistar rats. For example, mature rats showed a significant increase in body weight that was associated. In addition, mature rats showed an increase in the serum concentration of triglycerides, total cholesterol, and LDL cholesterol, which is characteristic of dyslipidemia. There was also an increase in serum glucose compared with the younger groups of animals. Therefore, aging Wistar rats appear to be an interesting model to study the changes related to metabolic syndrome.

Influence of Triiodothyronine and Dexamethasone on the Postnatal Development of Hepatic Eosine Transport in Rats

In male Wistar rats of different ages the influence of a three days pretreatment with triiodothyronine (T3, 100 micrograms/kg b.m.s.c.) or dexamethasone (0.4 mg/kg b.m.i.p.) on eosine accumulation of rat liver in vitro and biliary excretion of eosine in vivo was investigated. T3 stimulated the eosine accumulation in liver slices. This in vitro effect was not paralleled by higher serum elimination rates of eosine in vivo. Neither T3 nor dexamethasone could accelerate the maturation of the rate limiting excretion process for organic anions in developing rats.

Topographic Trace-Elemental Analysis in the Brain of Wistar Rats by X-ray Microfluorescence with Synchrotron Radiation

Knowledge about the spatial distribution and the local concentration of trace elements in tissues is of great importance, since trace elements are involved in many biological functions of living organisms. However, there are few methods available to measure the spatial (two (three)-dimensional) elemental distribution in animal brain. X-ray microfluorescence with synchrotron radiation is a multielemental mapping technique, which was used in this work to determine the topographic of iron, zinc and copper in coronal sections of female Wistar rats of different ages. Young (14 days old) and middle-aged (20 months old) rats (n = 8) were analyzed. The measurements were carried out at the XRF beam line at the Synchrotron Light National Laboratory (Campinas, Brazil). Two-dimensional scanning was performed in order to study the tendency of elemental concentration variation. The acquisition time for each pixel was 10 s/step and the step size was 300 microm/step in both directions. It was observed that the iron distribution was more conspicuous in the cortical area, thalamus and bellow the thalamus. On the other hand, the zinc distribution was more pronounced in the hippocampus. The iron, copper and zinc levels increased with advancing age. Therefore, this study reinforces the idea that these elements are involved in the chemical mechanisms of the brain that induce some neurological diseases, since they are also present in high levels in specific areas of the brain, such as the hippocampus and the substantia nigra of patients with these disorders.

Impairment of nutritional regulation of adipose triglyceride lipase expression with age

Fasting-induced lipolysis becomes less effective with age. We have studied whether nutritional regulation of adipose triglyceride lipase (ATGL)--with an important role in lipolysis in low energy states--is affected by age. Wistar rats of different ages (from 1 to 13 months) were distributed in control and fasted groups (14 h-food deprivation). ATGL mRNA expression was measured in different adipose depots at different ages and in only one depot at 13 months by reverse transcription (RT)-PCR. ATGL protein levels were determined at 3 and 7 months (not at 13 months) by western blot. Nonesterified fatty acid (NEFA), insulin and leptin levels were assessed in serum by enzymatic assays. ATGL expression was dependent on regional fat distribution, with higher levels in brown than in white adipose tissue depots; and was affected by age: ATGL mRNA was increased with age in the brown adipose tissue and was decreased in two of the studied white depots, the inguinal and retroperitoneal, not being affected in the epididymal and mesenteric. Age also affected ATGL nutritional regulation: fasting increased ATGL gene expression and protein levels in the different white adipose depots of the youngest rats (up to the age of 5 months), whereas there was no change in the oldest rats studied (7 and 13-months old). This was in agreement with the pattern of NEFA levels, which did not increase in serum of fasted rats in the oldest animals, whereas other homeostatic parameters, such as insulin and leptin, responded to fasting independently of age. ATGL expressed by brown adipose tissue was not affected by feeding conditions at any age. Nutritional regulation of ATGL expression in white adipose tissue is impaired with age, which could contribute to the increased difficulty for mobilizing lipids when animals are exposed to nutritional stress such as fasting.

Characterization of the Phosphate Units in Rat Dentin by Solid-State NMR Spectroscopy

Dentin samples of the incisor taken from Wistar rats of different ages are studied. A series of physical techniques are used to characterize the samples, with particular emphasis on 31P solid-state nuclear magnetic resonance. The structure of incisor dentin in rats can be described as apatite crystallites embedded in an amorphous matrix. We find that 19% of the apatite crystallites contain hydroxyl groups, which are distributed near the surface of the crystallites. The internal region of the crystallites is deficient in hydroxyl groups. As rats mature with age, there are several changes in the chemical composition of the incisor dentin: (i) the water content and phosporous amount in the amorphous matrix decrease; (ii) the amount of the phosphorus species in the apatite crystallites remains the same; and (iii) the loss of phosphorus species is accompanied by approximately the same loss of the calcium content.

Ontogenetic Changes in Glial Fibrillary Acid Protein Phosphorylation, Glutamate Uptake and Glutamine Synthetase Activity in Olfactory Bulb of Rats

Phosphorylation of the glial fibrillary acidic protein (GFAP) in hippocampal and cerebellar slices from immature rats is stimulated by glutamate. This effect occurs via a group II metabotropic glutamate receptor in the hippocampus and an NMDA ionotropic receptor in the cerebellum. We investigated the glutamate modulation of GFAP phosphorylation in the olfactory bulb slices of Wistar rats of different ages (post-natal day 15 = P15, post-natal day 21 = P21 and post-natal day 60 = P60). Our results showed that glutamate stimulates GFAP phosphorylation in young animals and this is mediated by NMDA receptors. We also observed a decrease in glutamate uptake at P60 compared to P15, a finding similar to that found in the hippocampus. The activity of glutamine synthetase was elevated after birth, but was found to decrease with development from P21 to P60. Together, these data confirm the importance of glutamatergic transmission in the olfactory bulb, its developmental regulation in this brain structure and extends the concept of glial involvement in glutamatergic neuron-glial communication.

P2-138 Evaluation of brain glycuronidation process in cholesterol fed wistar rats of different ages

P2-138 Evaluation of brain glycuronidation process in cholesterol fed wistar rats of different ages

Aging increases amyloid β-peptide-induced 8-iso-prostaglandin F 2α release from rat brain

In order to investigate whether amyloid β-peptide-induced oxidative damage in the brain could be related to aging, we studied the release of 8-iso-prostaglandin (PG)F 2α, a stable marker of cellular oxidative stress, in brain synaptosomes from Wistar rats of different ages (3, 6, 12, 18 months old), both basally and after amyloid β-peptide (1–40) perfusion. We found that basal release of 8-iso-PGF 2α was not significantly different among all age groups of rats. Either phospholipase A 2 activation induced by calcium ionophore A23187 (10 nM) or amyloid β-peptide (5 μM) did not modify isoprostane release, when these substances were used alone. In contrast, amyloid β-peptide (1–5 μM) preincubation caused a dose-dependent increase of A23187-stimulated 8-iso-PGF 2α release in each age group, which was also strikingly correlated to aging of rats. Furthermore, ferric ammonium sulfate stimulates isoprostane production to levels comparable to those induced by amyloid β-peptide. In conclusion, although 8-iso-PGF 2α production from rat brain synaptosomes is independent from aging in the basal state, aging renders neurons more vulnerable to amyloid β-peptide-induced oxidative toxicity.

Analysis of incisor pulp cell populations in Wistar rats of different ages

Pulp cell function and viability is important for maintaining tooth vitality throughout life. However, the effects of ageing on pulpal cell populations and pulp tissue remodelling are still unclear. The aim here was to quantify age-related cell-density changes in the pulp of rat incisor teeth, using histomorphometric analysis and ANOVA. Mandibular ( n=35) and maxillary ( n=34) incisors were carefully extracted from 20 Wistar rats aged between 1 and 18 months, fixed and processed for light microscopy. Cell counts were performed in mature and immature regions at both labial and lingual aspects of all teeth. Odontoblast and subodontoblast cell densities were reported per mm of pulp–dentine border and core fibroblast density per mm 2 pulp tissue. Irrespective of age, odontoblast and subodontoblast densities were lower in the immature than the mature regions of both maxillary and mandibular incisors ( P<0.001). However, in both regions odontoblast and subodontoblast densities decreased significantly with increasing age ( P<0.0001). The age-related reduction in odontoblasts was significantly greater in mature than immature regions ( P<0.02) but not influenced by other variables. In contrast, the age-related reduction in subodontoblasts was significantly different between mandibular and maxillary teeth ( P=0.012) but not influenced by site. Unlike odontoblasts and subodontoblasts, core fibroblasts showed small but significant increases with increasing age ( P<0.0001). These age-related reductions in the density of odontoblasts and subodontoblasts may partly explain the slower rate of secondary dentine secretion and decreased pulp repair activity associated with ageing.

Development of haemoglobin subtypes and extramedullary haematopoiesis in young rats. Effects of hypercapnic and hypoxic environment.

The influence of repeated hypoxia on the development of haemoglobin (Hb) subtypes and on extramedullary haematopoiesis (EMH) was investigated in young Wistar rats of different ages. The rats were exposed to hypercapnic/hypoxic and to "simple" hypoxic conditions. The results obtained were compared to those of an untreated age-matched control group. Different globin chains were measured using HPLC and time-of-flight (TOF) mass analysis. The number of EMH cells was evaluated by cell counting. By determining the proportions of alpha- and beta-chains, fetal, neonatal and mature types of globin chain composition could be differentiated. The beta-2 chain levels were significantly higher in hypercapnic/hypoxic environments than in the controls and simple hypoxic environments. The numbers of EMH cells in the two groups subjected to hypercapnia/hypoxia decreased significantly more slowly compared to the controls and simple hypoxia groups. Therefore, the development of Hb subtypes and the EMH activity in rats were influenced by both repeated hypercapnia and hypoxia.

Proliferation Activity and Number of Stromal (CFU-f) and Haemopoietic (CFUs) Stem Cells in Bone Marrow and Spleen of Rats of Different Ages

home Acta Veterinaria Brno Journal of the University of Veterinary Sciences Brno, Czech Republic Search:

Measurement of oxidatively induced base lesions in liver from Wistar rats of different ages

Mitochondrial and nuclear DNA were isolated from the livers of young (6–7 month) and old (23–24 month) Wistar rats and the levels of 10 different oxidatively induced lesions were analyzed by gas chromatography/mass spectrometry. This is the first study to measure several different oxidatively induced base lesions in both mitochondrial and nuclear DNA as a function of age. No significant age effects were observed for any lesion. Furthermore, contrary to expectations, we did not observe elevated levels of oxidatively induced base lesions in mitochondrial DNA. This contrasts with 50-fold differences reported for several lesions between mitochondrial and nuclear DNA from porcine liver (Zastawny et al., Free Radic. Biol. Med. 24:722–725, 1998). The fact that different lesion levels are observed even when similar techniques are employed emphasizes that the role of oxidative mitochondrial DNA damage and its repair in aging must continue to be the subject of intense investigation. Questions concerning endogenous levels of damage should be revisited as existing methods are improved and new methods become available.

Growth Hormone Gene Expression and Secretion in Aging Rats Is Age Dependent and Not Age-Associated Weight Increase Related

GH secretion declines with age in rats and humans and a reduction in GH gene expression has been demonstrated in aging rats. GH secretion also diminishes in obesity; thus, the aim of this study was to determine whether GH decrease in aging rats is due to body weight gain or to aging. Three groups of male Wistar rats of different ages were studied (young, 3 months; middle-aged, 11 months; old, 27 months). The middle-aged group was established on a statistical analysis and corresponded to the youngest age at which body weight was not significantly different from the old (27 month) group. Thus, by using this group as control for comparison with animals with the same weight and an older age, the effects due to aging itself could be determined. Body weight (g, mean ±sd) 3 months: 361 ± 5.6; 11 months: 713 ± 39; 27 months: 635 ± 38. In comparison with 3-month-old rats, the 11-month-old animals showed no difference in pituitary GH messenger RNA (mRNA) accumulation and pituitary and serum IR-GH levels. Similarly IGF-I.a, IGF-I.b mRNA transcripts and IGFBP-3 mRNA accumulation in the liver showed no significant differences between the two groups. On the contrary, when the 27-month-old rats were compared with the 11-month-old animals, lower levels of pituitary GH mRNA and serum and pituitary IR-GH were found. Pituitary GH mRNA decreased 37.5 ± 7.7% P < 0.001, pituitary IR-GH content diminished (5.2 ± 3.4 vs. 55 ± 10.7 ng/mg of protein, P < 0.001) and serum IR-GH decreased (3.5 ± 1.8 vs. 12.5 ± 4.2 ng/ml, P < 0.01). Liver IGF-I.a and IGF-I.b mRNA transcripts accumulation and serum IGF-I were significantly diminished. IGF-I.b mRNA accumulation decreased 35.8 ± 1.2% P < 0.05 and IGF-I.a 36 ± 5.6% P < 0.05; serum IR-IGF-I levels diminished (759 ± 152 vs. 1327 ± 67 ng/ml, P < 0.05). Liver IGFBP-3 mRNA accumulation decreased 79 ± 4.2% P < 0.001. These results indicate that the decrease in GH gene expression and secretion, as well as the expression of genes induced by GH such as IGF-I and IGFBP-3, is due to aging and not to the increase in body weight that takes place with aging.

Growth hormone gene expression and secretion in aging rats is age dependent and not age-associated weight increase related.

GH secretion declines with age in rats and humans and a reduction in GH gene expression has been demonstrated in aging rats. GH secretion also diminishes in obesity; thus, the aim of this study was to determine whether GH decrease in aging rats is due to body weight gain or to aging. Three groups of male Wistar rats of different ages were studied (young, 3 months; middle-aged, 11 months; old, 27 months). The middle-aged group was established on a statistical analysis and corresponded to the youngest age at which body weight was not significantly different from the old (27 month) group. Thus, by using this group as control for comparison with animals with the same weight and an older age, the effects due to aging itself could be determined. Body weight (g, mean +/- sD) 3 months: 361 +/- 5.6; 11 months: 713 +/- 39; 27 months: 635 +/- 38. In comparison with 3-month-old rats, the 11-month-old animals showed no difference in pituitary GH messenger RNA (mRNA) accumulation and pituitary and serum IR-GH levels. Similarly IGF-I.a, IGF-I.b mRNA transcripts and IG-FBP-3 mRNA accumulation in the liver showed no significant differences between the two groups. On the contrary, when the 27-month-old rats were compared with the 11-month-old animals, lower levels of pituitary GH mRNA and serum and pituitary IR-GH were found. Pituitary GH mRNA decreased 37.5 +/- 7.7% P < 0.001, pituitary IR-GH content diminished (5.2 +/- 3.4 vs. 55 +/- 10.7 ng/mg of protein, P < 0.001) and serum IR-GH decreased (3.5 +/- 1.8 vs. 12.5 +/- 4.2 ng/ml, P < 0.01). Liver IGF-I.a and IGF-I.b mRNA transcripts accumulation and serum IGF-I were significantly diminished. IGF-I.b mRNA accumulation decreased 35.8 +/- 1.2% P < 0.05 and IGF-I.a 36 +/- 5.6% P < 0.05; serum IR-IGF-I levels diminished (759 +/- 152 vs. 1327 +/- 67 ng/ml, P < 0.05). Liver IGFBP-3 mRNA accumulation decreased 79 +/- 4.2% P < 0.001. These results indicate that the decrease in GH gene expression and secretion, as well as the expression of genes induced by GH such as IGF-I and IGFBP-3, is due to aging and not to the increase in body weight that takes place with aging.