Age-related and steroid induced changes in the histones of the quail liver

Histones were extracted from the liver of young, adult and old Japanese quails. Both linker and core histones were found to vary with age. An extra band, H3X, was found between H2A and H4. Its level is higher in young and old birds in comparison to that of the adult. H3X shows interesting changes under steroid induction. Its level is higher in progesterone administered young birds. In adult and old birds, it is higher in progesterone treated (P) and progesterone primed estradiol administered (P+E) birds, and lower in all estradiol (E) and estradiol primed progesterone administered (E+P) birds. The relative levels of H3X in the steroid administered birds also vary with age. Such changes may influence chromatin conformation and gene expression.     

Age-related regulation of mouse brain cortex adrenoceptors following camphor vapor exposition

The paper deals with the ability of adrenergic receptors (AR) of mouse brain cortex to be differentially regulated in response to single or multiple expositions to camphor vapor. The regulation of alpha- and beta-adrenoceptors has been studied in young and old Balb/c-nu mice. Results confirm the decrease of total beta-adrenoceptor density previously observed in untreated mice with advancing age; in addition, receptor density decreases in both young and old mice after a single exposition to camphor vapor, followed by an adaptation after multiple stimuli. The beta1, subtype is mainly responsible for density decrease in young animals, while both beta1, and beta2 subtypes contribute to the decrease in old mice. On the contrary, beta2 subpopulation gives the major contribution to the adaptive recovery in both young and old mice. alpha-Adrenoceptors also show an age-related decrease in the control group; after a single exposition they show an increased density with the exception of alpha1-subset in the young group. Repeated expositions lead to a rather general adaptive response towards pre-stimuli conditions. The differential behaviour of receptor subtypes in response to camphor vapor exposition can be related to the differential alterations of receptor characteristics observed during aging and also suggests a possible mechanism through which these alterations may occur.     

Age-related base excision repair activity in mouse brain and liver nuclear extracts

To assess DNA repair activity relative to age, in vitro base excision repair assays were performed using brain and liver nuclear extracts prepared from mice of various ages. An 85% decline in repair activity was observed in brain nuclear extracts and a 50% decrease in liver nuclear extracts prepared from old mice compared with 6-day-old mice. Brain nuclear extracts prepared from old mice showed a decreased abundance of DNA polymerase-beta, but the addition of purified protein did not restore base excision repair activity. Abundances of other tested base excision repair proteins did not change relative to age. The conclusion is that, during aging, a decline in DNA repair could contribute to increased levels of DNA damage and mutagenesis.     

Age-related change in the multiple unit activity of the rat brain parietal cortex and the effect of centrophenoxine

In this study, spontaneous multiple unit activity (MUA, action potentials derived simultaneously from a number of neurons in a given brain region) was recorded through electrodes chronically implanted in the parietal cerebral cortex of the rats of 1, 3, 6, 9, 12, and 26 months of age (cross-sectional study). Electrophysiological recordings were obtained from unrestrained conscious rats using standard techniques. The results indicated that multiple unit activity was decreased with aging (senescence). Maximum firing rate (MUA counts) was found at the age of 3 months. At 6 months of age, the MUA was decreased by about 30%, while during 6 to 12 months of age the activity seemed to remain unchanged. At 26 months of age the firing rate was, however, further decreased (about 40%). Centrophenoxine administration led to an increase in MUA in the rats of 12 and 26 months of age. The results, thus, further showed that centrophenoxine, a nootropic drug known for its antiaging effects in experimental animals as well as in humans, also manifested beneficial effects electrophysiologically. The data presented in this work are new and significant, since although age effects on gross electrophysiological signals (EEG, evoked potentials, etc.) are known, the aging changes in cellular level electrophysiological signals (action potentials) have not been generally studied particularly in conscious animals.     

Age-related changes in brain neurotransmission

In experiments on 2-, 10- and 22-month-old rats it was found that the Bmax values of dopamine (DA2), serotonin (5-HT1) and enkephalin (Enk) receptors as well as the 5-HT level in the three brain regions (cortex, striatum and hypothalamus) decreased with age; the DA level in the brain cortex and striatum and the noradrenaline (NA) content in the brain cortex decreased, while the NA level in the striatum and the 5-hydroxyindolacetic acid (5-HIAA) level in the brain cortex and the striatum as well as the MAO-T and MAO-A activities in the three brain structures increased. It is suggested that these and other changes observed in brain neurotransmission are an important element in the neurochemical bases of the age-related changes in behavior.     

Age-related changes in the corneal endothelium of the mouse

The endothelial cells of the C57BL/6J mouse cornea show a progressive age-related increase in cell area, and an increasing departure from the initial hexagonal form. Mean endothelial surface areas were 304, 386, 458, 499, and 653 micron2 for mice of ages 1, 4, 11, 22, and 27 months, respectively. Increasing cell areas are interpreted to represent a spreading and thinning of surviving cells to compensate for cell loss. These age-related changes correspond to those previously observed in the rat, although the rat endothelial cells tend to have smaller cell areas and show less variation at each age studied.     

Age-related autophagy alterations in the brain of senescence accelerated mouse prone 8 (SAMP8) mice

Autophagy is responsible for the degradation of long-lived proteins and damaged organelles intracellular, even extracellular,and autophagy is proved to have relationship with Alzheimer's disease (AD) and aging. The senescence accelerated mouse prone 8 (SAMP8) was a non-genetically modified mice widely used as a rodent model of aging and senile dementia. However, little was known about the age-related changes of autophagy in the brain of SAMP8 mice. To better understand the precise relationship between aging, autophagy and neurodegeneration, we explored the time course of cognitive ability, ubiquitin-positive inclusions, ultrastructure of neurons and detected the expression of LC3 and Beclin 1 protein in different brain regions of 2, 7 and 12-month-old SAMP8 and SAMR1 mice. We found that 7 and 12-month-old SAMP8 mice presented cognitive decline and ubiquitinated proteins enhanced. In the hippocampal neurons of 12-month-old SAMP8 mice, lots of dense clumps and autophagic vacuoles were found in the cytoplasm and axons. The LC3-II expression showed an increase in hippocampus and cortex of 7 and 12-month-old SAMP8 mice. The expression of Beclin 1 displayed a significant increase in 7 months old and a decline in 12 months old mice. Based on these data, we suggest that the autophagic activity maybe increase reactively at the beginning of AD and then showed a decline with aging, and the pathological changes of 12-month-old SAMP8 mice are more similar to the late-onset AD in the perspective of autophagy.     

Age-related alterations in the heat-stability of mouse heart phosphorylase

Myocardial phosphorylase from young and old mice has been examined with respect to its thermal lability properties. It has been shown that phosphorylase from the hearts of old animals is more resistant to heat as compared to the enzyme from young hearts. This increase in thermal stability seems to be correlated with an increase in the less active tetrametric form of the enzymes during aging. Sucrose density centrifugation profiles indicate that upon heating the amount of dimer stays relatively constant in the old heart since the tetramer is probably being broken down into its more active dimeric form. This increase in the tetrameric form of phosphorylase in the old heart may help to explain the increased susceptibility of the old heart to many acute stresses.     

Age-related change in skeletal muscle blood flow in the rat

Anesthetized adult and senescent male Fischer 344 rats were instrumented for stimulation of in situ plantar flexor muscles and blood flow measurement by the tracer microsphere technique. After determination of optimum length and maximum tetanic force, muscles were stimulated to contract at the rate of 120 tetani/min. Senescent rats displayed significantly lower muscle blood flow and greater muscle fatigue than younger rats. Infusion of a nonspecific vasodilator in resting anesthetized rats also revealed a significantly lower potential to increase muscle blood flow in the senescent rats. Lower muscle blood flow of senescent rats during muscle contractions might be responsible, at least in part, for decreased performance of muscles of senescent male rats.     

Age-related change in human gastric mucosal energy metabolism

Many investigators have reported a decrease in mucosal blood flow resulting in impairment of gastric mucosal energy metabolism in animal experiments. Recently, endoscopic studies using reflectance spectrophotometry and laser Doppler flowmetry have indicated that gastric mucosal blood flow in humans decreases with age. However, changes in energy metabolism in human gastric mucosa with age remains obscure. In this study, we measured adenine nucleotides in biopsy samples from human gastric mucosa, using high-performance liquid chromatography, and investigated changes in energy metabolism with age in subjects proven normal endoscopically. Energy charge (EC = (ATP + 1/2 ADP)/ATP + ADP + AMP) in the gastric antral and body mucosa showed decrease with age. When the subjects were divided into two groups, less than and more than 65 years old, the EC level was significantly lower in the latter than the former in both antral and body mucosa (0.65 +/- 0.06 versus 0.74 +/- 0.03 in the antrum, 0.73 +/- 0.04 versus 0.79 +/- 0.04 in the body) and significantly less in the antral mucosa than in body mucosa in both groups. The adenosine triphosphate (ATP) level in the older group showed a significant decrease (6.48 +/- 1.14 versus 9.63 +/- 1.92 in the antrum, 8.59 +/- 1.64 versus 10.60 +/- 2.13 in the body) compared with those less than 65 years old. In the antral mucosa of the older group the adenosine diphosphate (ADP) level was also significantly lower than that in the group less than 65. In conclusion, in the elderly, the energy metabolism in human gastric mucosa is impaired, and this may weaken their defensive mechanism.     

Age-related differences in the response of the brain to dietary melatonin

The aged brain is prone to excessive levels of immune activity, not initiated by an acute response to an extrinsic agent. While dietary melatonin is reported to attenuate the extent of expression of proinflammatory genes, little is known about the extent to which these changes can be translated into altered levels of corresponding proteins. The baseline levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-1 alpha, were greater in older (~29 months old) compared to younger (~7 months old) mouse brains. Acute (3 h) exposure to lipopolysaccharide (LPS) induced activation of nuclear factor kappa B (NF-κB), but not inflammatory cytokines in the brain. The serum level of TNF-α was increased after LPS injection, indicating a systemic immune response to the bacterial cell wall component. Dietary melatonin (40 ppm for 9.3 weeks) did not prevent LPS-induced changes in younger animals but caused an increased systemic TNF-α response in older mice. Melatonin did reduce markers of carbonyl formation in brain proteins of young animals and nitrosylative damage to peptide-bound amino acid residues, in the brains of older animals. Acute LPS challenge did not significantly affect these oxidative markers. Thus, despite lack of clear evidence of attenuation of the NF-κB–cytokine inflammatory trajectory within the CNS by melatonin, this agent did show a protective effect against free radical-initiated injury to amino acid residues within proteins. The results illustrate that previously reported changes in gene expression following melatonin treatment need not be closely paralleled by corresponding changes in protein content.     

快速老化小鼠行为学增龄性研究

目的 对快速老化小鼠SAMP8老化征象、焦虑状况及学习记忆能力的增龄性变化进行系统研究,为推广该模型在老化研究中的应用提供较全面的实验依据.方法 选用雄性4、8、12月龄SAMP8,以同龄同性别正常老化的SAMR1为对照,应用老化度评分、广场实验、高架十字迷宫实验及Morris水迷宫测试SAMP8的老化度、焦虑度和学习记忆等行为学的增龄性变化.结果 与SAMR1比较,SAMP8在4月龄尚未表现出明显的学习记忆障碍(P＞0.05),8月龄、12月龄明显加重(P＜0.05,P＜0.01);活动度检测发现8月龄SAMP8活动度增加显著(P＜0.01),对危险的识别度降低(P＜0.001);12月龄的SAMP8进一步加重,并存在明显的增龄性老化体征(P＜0.001)和焦虑情绪.结论 SAMP8随增龄存在快速老化的特征,证实SAMP8是研究老化、老年性痴呆等疾病的理想模型.     

Age-related functional alteration of mouse liver ribosomes

The in vitro functional capacity of the mouse liver protein synthesis machinery was studied as a function of age. Polysomes from young (one-three months old) and old (18–24 months old) C57BL/6J mice were incubated under standard conditions in a ribosome-free reticulocyte lysate containing [³H]-leucine. The incorporation of radioactivity into hot TCA-insoluble material was measured as a function of time and kinetic curves were compared. A drastic age-related decrease in the initial rate of leucine incorporation was observed when the total ribosomal fraction (containing the whole range of ribosomal aggregates including subunits and single ribosomes) was assayed. When “heavy polysomes” (fractions from which subunits and single ribosomes had been excluded) were compared, the same difference was observed. This latter result indicated that the observed alteration may be attributed to actively translating ribosomes. Results from experiments using inhibitors of initiation suggest that the observed age-related alteration can be attributed to a reduced capacity of ribosomes from older animals to sustain reinitiation.     

Age-related change in the reducible cross-link of human skin and aorta collagens

Age-related changes in the reducible cross-links of soluble and insoluble collagens from the human skin and aorta were evaluated. Histidinohydroxymerodemosine decreased with age up to the fifth decade and then remained constant in the insoluble skin collagen but could not be detected in the insoluble aorta collagen. Dihydroxylysinonorleucine could be observed, if in a small amount, in the insoluble aorta collagen but not in both the soluble and insoluble skin collagens. Hydroxylysinonorleucine seemed to be present in only a small amount, although coeluting unknown substances made it difficult to evaluate correctly. Two unknown components decreasing with age were found; the one in the insoluble skin collagen and the other in the insoluble aorta collagen. Difference in reducible cross-link was indicated between the skin and aorta collagens.     

Age-related natural change trend of important hormones in Chinese population

正Objective To reclarify the natural change trend of several hormones with age in Chinese population.Meth-o dsA cross-sectional survey was performed including5 935 healthy individuals (2 286 males and 3 649 females) in the final statistical analysis. All participants received questionnaire survey, anthropometric index and laboratory tests including sex-related hormones, insulin,     

Age-related change of endocytic receptors megalin and cubilin in the kidney in rats

Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.     

Age-related changes in lipid and carbohydrate metabolism of the genetically obese mouse

Obese mice (C57BL/6J ob/ob) and their lean controls were studied longitudinally from immediately post-weaning until 62 wk of age, at which time the experiment was terminated. The dynamic nature of the metabolic aberrations of the obese mouse syndrome was clearly demonstrated. Obese mice were hyperinsulinemic at all ages yet the concentration of glucose in plasma was elevated only at 5-20 wk and 63 wk of age, but was similar to that of lean mice at 20-60 wk of age. Triacylglycerols accumulated in the liver of obese mice between 5 and 18 wk of age to a level that was 20-fold greater than that found in the age-matched lean control. A decreased concentration of DNA/g of liver was also found in 5-18 wk-old obese mice, indicative of an enlarged hepatocyte. With the exception of 5-wk-old animals, total DNA per liver was increased in obese mice when compared to the lean control throughout the profile. Following the peak in 18-wk-old mice, the hepatic content of triacylglycerols precipitously fell so that at 45 wk of age its concentration in obese mice was similar to that of the lean control. Plasma free fatty acid levels as well as liver glycogen content were comparable in obese mice and their lean controls throughout the profile. In obese mice older than 45 wk of age, the content of triacylglycerols in plasma was significantly lower than that of the age-matched lean control while an accumulation of liver triacylglycerols was again found in obese mice. Myocardial triacylglycerols were elevated in obese mice when compared to the lean control at all ages. The longitudinal metabolic profile of the obese mouse developed in the present study clearly demonstrates the dynamic nature of the deviations in carbohydrate and lipid metabolism in this animal model of human obesity and insulin resistance.     

Age-related decline in cell-mediated immunity in the C58 leukemic mouse strain

The leukemia-prone C58 strain of mouse was examined for age-related changes in cellular immune function. Proliferative responses of lymphocytes to autologous and allogeneic stimulator cells [autologous mixed lymphocyte response (AMLR) and mixed lymphocyte response (MLR), respectively] and to mitogens were tested both prior to and around the usual age of disease onset which occurs at 7-8 months. Leukemia in these animals was defined by elevated peripheral blood and splenic white blood cell counts. The AMLR declined greater than 30% by 6-7 months of age and was virtually absent by 8 months of age even in animals that were not overtly leukemic. The MLR declined precipitously (greater than 95%) at 9 months of age. Both declines occurred at a younger age in C58 mice than in nonleukemic strains. Mixing experiments with cells from young and old animals indicate a defect in the Ly 1+23-, L3T4+ responding T cells. No evidence indicating a role for suppressor cell activity in this decline of cell-mediated immunity could be found. Deficiencies in cytokine (IL-2 and IL-1) production were not observed except in the oldest mice tested. Around the usual time of disease onset, splenic natural killer (NK) cell activity declines sharply even in nonleukemic mice. Cell-mixing experiments showed no evidence of suppressor cell activity by spleen cells from older mice, leukemic or nonleukemic, on the NK cell activity of young adult animals. Interferon alpha, beta treatment enhanced the NK activity of cells from old mice but did not restore the level of activity seen in young mice. Evidence has therefore been found for a premature decline in cellular immune function in two responses with proposed immunoregulatory roles, the AMLR and NK cell activity. It is possible that their decline could play a predisposing role in the onset of this retroviral leukemia or that these cell populations may be the target of the retrovirus.