F5
Coagulation factor V precursor (Activated protein C cofactor) (Proaccelerin, labile factor) [Contains: Coagulation factor V heavy chain; Coagulation factor V light chain]
Publications[править]
A DNA methylation (DNAm) signature derived from 353 CpG sites (the Horvath clock) has been proposed as an epigenetic measure of chronological and biological age. This epigenetic signature is accelerated in diverse tissue types in various disorders, including non-alcoholic steatohepatitis, and is associated with mortality. Here, we assayed whole blood DNAm to explore age acceleration in patients with primary sclerosing cholangitis (PSC). Using the MethylationEPIC BeadChip (850K) array, DNAm signatures in whole blood were analyzed in 36 patients with PSC enrolled in a 96-week trial of simtuzumab (Ishak F0-1, n = 13; F5-6, n = 23). Age acceleration was calculated as the difference between DNAm age and chronological age. Comparisons between patients with high and low age acceleration (≥ [i]vs[/i]. < the median) were made and Cox regression evaluated the association between age acceleration and PSC-related clinical events ([i]e.g.[/i] decompensation, cholangitis, transplantation). Age acceleration was significantly higher in patients with PSC compared to a healthy reference cohort (median, 11.1 years, [i]p[/i] <2.2 × 10 ). In PSC, demographics, presence of inflammatory bowel disease, and ursodeoxycholic acid use were similar between patients with low and high age acceleration. However, patients with high age acceleration had increased serum alkaline phosphatase, gamma glutamyltransferase, alanine aminotransferase, enhanced liver fibrosis test scores, and greater hepatic collagen and α-smooth muscle actin expression on liver biopsy (all [i]p[/i] <0.05). Moreover, patients with high age acceleration had an increased prevalence of cirrhosis (89% [i]vs.[/i] 39%; [i]p[/i] = 0.006) and greater likelihood of PSC-related events (hazard ratio 4.19; 95% CI 1.15-15.24). This analysis of blood DNAm profiles suggests that compared with healthy controls, patients with PSC - particularly those with cirrhosis - exhibit significant acceleration of epigenetic age. Future studies are required to evaluate the prognostic implications and effect of therapies on global methylation patterns and age acceleration in PSC. An epigenetic clock based on DNA methylation has been proposed as a marker of age. In liver diseases such as non-alcoholic steatohepatitis, age acceleration based on this epigenetic clock has been observed. Herein, we show that patients with primary sclerosing cholangitis have marked age acceleration, which is further accentuated by worsening fibrosis. This measure of age acceleration could be a useful marker for prognostication or risk stratification in primary sclerosing cholangitis.
Keywords
- ALP, alkaline phosphatase
- ALT, alanine aminotransferase
- Aging
- BMI, body mass index
- DNAm, DNA methylation
- ELF, enhanced liver fibrosis
- FDR, false discovery rate
- GGT, gamma-glutamyltransferase
- IBD, inflammatory bowel disease
- IL, interleukin
- LOXL2, lysyl oxidase-like-2
- NASH, non-alcoholic steatohepatitis
- PSC, primary sclerosing cholangitis
- SMA, smooth muscle actin
- UDCA, ursodeoxycholic acid
- biomarker
- inflammatory bowel disease
- primary sclerosing cholangitis
- prognosis
- ursodeoxycholic acid
Chronic and extensive exposure of ultraviolet (UV)-irradiation causes human skin sunburn, inflammation, or photoaging, which is associated with downregulated collagen synthesis. This study investigated the effects of fermented blackberry ([i]Rubus fruticosus[/i] B., FBB) by [i]Lactobacillus plantarum[/i] JBMI F5 (LP) on UVB-induced photoaging in human foreskin fibroblast (Hs68) as well as in SKH-1 hairless mice. FBB pretreatment inhibited UVB-mediated type-1 procollagen degradation, matrix metalloproteinase (MMP)-1 and MMP-2 protein expression, and suppressed nuclear factor-κB (NF-κB) activation as well as mitogen-activated protein kinase (MAPK) phosphorylation in Hs68. In addition, FBB administration diminished the wrinkle formation in dorsal skin and epidermal thickening in UVB-irradiated hairless mice. Moreover, UVB-induced Type-1 procollagen reduction and antioxidant enzyme inactivation were reversed by FBB administration. These results suggest that FBB may have antiphotoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of reactive oxygen species and related MAPK and NF-κB signaling. Therefore, FBB can be a potential candidate for protecting skin aging against UV irradiation.
MeSH Terms
- Animals
- Cell Line
- Cell Survival
- Female
- Fermentation
- Fibroblasts
- Foreskin
- Fruit
- Lactobacillus plantarum
- Male
- Mice
- Mice, Hairless
- Plant Extracts
- Rubus
- Skin Aging
- Ultraviolet Rays
Keywords
- Lactobacillus plantarum
- MMPs
- fermented blackberry
- photoaging
- skin aging
- type I procollagen
The use of DNA methylation (DNAm) for chronological age determination has been widely investigated within the last few years for its application within the field of forensic genetics. The majority of forensic studies are based on blood, saliva, and buccal cell samples, respectively. Although these types of samples represent an extensive amount of traces found at a crime scene or are readily available from individuals, samples from other tissues can be relevant for forensic investigations. Age determination could be important for cases involving unidentifiable bodies and based on remaining soft tissue e.g. brain and muscle, or completely depend on hard tissue such as bone. However, due to the cell type specificity of DNAm, it is not evident whether cell type specific age-dependent CpG positions are also applicable for age determination in other cell types. Within this pilot study, we investigated whether 13 previously selected age-dependent loci based on whole blood analysis including amongst others ELOVL2, TRIM59, F5, and KLF14 also have predictive value in other forensically relevant tissues. Samples of brain, bone, muscle, buccal swabs, and whole blood of 29 deceased individuals (age range 0-87 years) were analyzed for these 13 age-dependent markers using massive parallel sequencing. Seven of these loci did show age-dependency in all five tissues. The change of DNAm during lifetime was different in the set of tissues analyzed, and sometimes other CpG sites within the loci showed a higher age-dependency. This pilot study shows the potential of existing blood DNAm markers for age-determination to analyze other tissues than blood. We identified seven known blood-based DNAm markers for use in muscle, brain, bone, buccal swabs, and blood. Nevertheless, a different reference set for each tissue is needed to adapt for tissue-specific changes of the DNAm over time.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Bone and Bones
- Brain Chemistry
- Child
- Child, Preschool
- CpG Islands
- DNA Methylation
- Female
- Genetic Markers
- High-Throughput Nucleotide Sequencing
- Humans
- Infant
- Infant, Newborn
- Linear Models
- Male
- Middle Aged
- Mouth Mucosa
- Muscle, Skeletal
- Pilot Projects
- Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
- Proof of Concept Study
- Saliva
- Sequence Analysis, DNA
- Young Adult
Keywords
- Age determination
- DNA methylation
- Forensic epigenetics
- Massive parallel sequencing
One of the most widely used organic UV filters, 4-methylbenzylidene camphor (4-MBC), is present at high concentrations in offshore waters. The marine copepod Tigriopus japonicus was exposed to different concentrations of 4-MBC (i.e., 0, 0.5, 1, 5 and 10μgL ) for 4 consecutive generations (F0-F3) to evaluate the impact of 4-MBC on marine ecosystems. The results showed that in the F0 generation, 4-MBC caused significant lethal toxicity in T. japonicas at concentrations of 5 and 10μgL and the nauplii were more sensitive to 4-MBC toxicity than the adults. However in the F1-F3 generations, 4-MBC exposure did not affect the survival rate. The hatching rate and the developmental duration from the nauplii to the copepodite (N-C) and from the nauplii to adult (N-A) decreased significantly in the F1-F2 generations and in the F2-F3 generations, respectively, even at the lowest exposure concentration (0.5μgL ). In the subsequent two generations (i.e., the F4-F5 generations) of recovery exposure in clean seawater, the growth rates of the original 4-MBC exposure groups were still faster than the control in both the N-C and N-A stages, suggesting possible transgenerational genetic and/or epigenetic changes upon chronic 4-MBC exposure. The expression of the ecdysone receptor gene was up-regulated by 4-MBC, which was consistent with the decrease of the N-C/N-A duration. In addition, 4-MBC may induce oxidative stress and trigger apoptosis in T. japonicas, resulting in developmental, reproductive and even lethal toxicity. A preliminary risk assessment suggested that under environmentally realistic concentrations, 4-MBC had significant potential to pose a threat to marine crustaceans and marine ecosystems.
MeSH Terms
- Animals
- Camphor
- Copepoda
- Female
- Longevity
- Reproduction
- Water Pollutants, Chemical
Keywords
- 4-Methylbenzylidene camphor
- Aquatic toxicity
- Multigenerational toxicity
The use of DNA methylation (DNAm) to obtain additional information in forensic investigations showed to be a promising and increasing field of interest. Prediction of the chronological age based on age-dependent changes in the DNAm of specific CpG sites within the genome is one such potential application. Here we present an age-prediction tool for whole blood based on massive parallel sequencing (MPS) and a random forest machine learning algorithm. MPS allows accurate DNAm determination of pre-selected markers and neighboring CpG-sites to identify the best age-predictive markers for the age-prediction tool. 15 age-dependent markers of different loci were initially chosen based on publicly available 450K microarray data, and 13 finally selected for the age tool based on MPS (DDO, ELOVL2, F5, GRM2, HOXC4, KLF14, LDB2, MEIS1-AS3, NKIRAS2, RPA2, SAMD10, TRIM59, ZYG11A). Whole blood samples of 208 individuals were used for training of the algorithm and a further 104 individuals were used for model evaluation (age 18-69). In the case of KLF14, LDB2, SAMD10, and GRM2, neighboring CpG sites and not the initial 450K sites were chosen for the final model. Cross-validation of the training set leads to a mean absolute deviation (MAD) of 3.21 years and a root-mean square error (RMSE) of 3.97 years. Evaluation of model performance using the test set showed a comparable result (MAD 3.16 years, RMSE 3.93 years). A reduced model based on only the top 4 markers (ELOVL2, F5, KLF14, and TRIM59) resulted in a RMSE of 4.19 years and MAD of 3.24 years for the test set (cross validation training set: RMSE 4.63 years, MAD 3.64 years). The amplified region was additionally investigated for occurrence of SNPs in case of an aberrant DNAm result, which in some cases can be an indication for a deviation in DNAm. Our approach uncovered well-known DNAm age-dependent markers, as well as additional new age-dependent sites for improvement of the model, and allowed the creation of a reliable and accurate epigenetic tool for age-prediction without restriction to a linear change in DNAm with age.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Algorithms
- CpG Islands
- DNA Methylation
- Genetic Markers
- High-Throughput Nucleotide Sequencing
- Humans
- Machine Learning
- Middle Aged
- Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
- Sequence Analysis, DNA
- Young Adult
Keywords
- Age prediction
- DNA methylation
- Machine learning
- Massive parallel sequencing
The aphid species Sitobion avenae and Rhopalosiphum padi are the most important pests in wheat growing regions of many countries. In this study, we investigated the sublethal effects of imidacloprid on fecundity, longevity, and enzyme activity in both aphid species by comparing 3-h exposure for one or three generations. Our results indicated that 3-h exposure to sublethal doses of imidacloprid for one generation had no discernible effect on the survival, fecundity, longevity, or enzyme activity levels of aphids. However, when pulse exposures to imidacloprid were sustained over three generations, both fecundity and longevity were significantly decreased in both S. avenae and R. padi. Interestingly, the fecundity of R. padi had almost recovered by the F5 generation, but its longevity was still deleteriously affected. These results indicated that R. padi laid eggs in shorter time lags and has a more fast resilience. The change in reproduction behavior may be a phenomenon of R. padi to compensate its early death. If this is stable for the next generation, it means that the next generation is more competitive than unexposed populations, which could be the reason underlying population outbreaks that occur after longer-term exposure to an insecticide. This laboratory-based study highlights the sublethal effects of imidacloprid on the longevity and fecundity of descendants and provides an empirical basis from which to consider management decisions for chemical control in the field.
MeSH Terms
- Acetylcholinesterase
- Animals
- Aphids
- Fertility
- Gene Expression Regulation
- Imidazoles
- Insect Proteins
- Longevity
- Neonicotinoids
- Nitro Compounds
- Time Factors
Keywords
- aphid
- enzyme activity
- fecundity
- imidacloprid
- sublethal effects
- survival
Cardiovascular and metabolic traits (CMT) are influenced by complex interactive processes including diet, lifestyle, and genetic predisposition. The present study investigated the interactions of these risk factors in relation to CMTs in the Turkish population. We applied bootstrap agglomerative hierarchical clustering and Bayesian network learning algorithms to identify the causative relationships among genes involved in different biological mechanisms (i.e., lipid metabolism, hormone metabolism, cellular detoxification, aging, and energy metabolism), lifestyle (i.e., physical activity, smoking behavior, and metropolitan residency), anthropometric traits (i.e., body mass index, body fat ratio, and waist-to-hip ratio), and dietary habits (i.e., daily intakes of macro- and micronutrients) in relation to CMTs (i.e., health conditions and blood parameters). We identified significant correlations between dietary habits (soybean and vitamin B12 intakes) and different cardiometabolic diseases that were confirmed by the Bayesian network-learning algorithm. Genetic factors contributed to these disease risks also through the pleiotropy of some genetic variants (i.e., F5 rs6025 and MTR rs180508). However, we also observed that certain genetic associations are indirect since they are due to the causative relationships among the CMTs (e.g., APOC3 rs5128 is associated with low-density lipoproteins cholesterol and, by extension, total cholesterol). Our study applied a novel approach to integrate various sources of information and dissect the complex interactive processes related to CMTs. Our data indicated that complex causative networks are present: causative relationships exist among CMTs and are affected by genetic factors (with pleiotropic and non-pleiotropic effects) and dietary habits.
MeSH Terms
- Aging
- Anthropometry
- Bayes Theorem
- Cardiovascular Diseases
- Diet
- Energy Metabolism
- Feeding Behavior
- Female
- Genetic Predisposition to Disease
- Humans
- Life Style
- Lipid Metabolism
- Lipoproteins, LDL
- Male
- Middle Aged
- Risk Factors
- Turkey
- Waist-Hip Ratio
Keywords
- Cardiometabolic traits
- Diet
- Genetic predisposition
- Interactive mechanisms
- Turkey
In Moscow region long-livers we have studied distribution of LPL, CETP, APOE, F2, F5, F7, F13, FGB, ITGA2, ITGB3, PAI-1, MTHFR, MTRR, HLA-DRB1, HLA-DQA1, HLA-DQB1 genes polymorphisms, associated with predisposition to age pathology. Long-livers are characterized by favorable course of cardiovascular diseases accompanied by certain genetic factors. We have established that genotype H-H- of LPL, allele epsilon2 of APOE, genotype CC of MTHFR (677C > T), genotype TC of ITGB3, genotype GA of FGB, HLA-DRB1*11 positively correlate with longevity.
MeSH Terms
- Aged
- Aged, 80 and over
- Alleles
- Cardiovascular Diseases
- Female
- Gene Frequency
- Genetic Markers
- Genetic Predisposition to Disease
- Genotype
- Humans
- Longevity
- Male
- Moscow
- Polymorphism, Genetic
- Prevalence
- Urban Population
Visual working memory (VWM) is a core cognitive system with a highly limited capacity. The present study is the first to examine VWM capacity limits in early development using functional neuroimaging. We recorded optical neuroimaging data while 3- and 4-year-olds completed a change detection task where they detected changes in the shapes of objects after a brief delay. Near-infrared sources and detectors were placed over the following 10-20 positions: F3 and F5 in left frontal cortex, F4 and F6 in right frontal cortex, P3 and P5 in left parietal cortex, and P4 and P6 in right parietal cortex. The first question was whether we would see robust task-specific activation of the frontal-parietal network identified in the adult fMRI literature. This was indeed the case: three left frontal channels and 11 of 12 parietal channels showed a statistically robust difference between the concentration of oxygenated and deoxygenated hemoglobin following the presentation of the sample array. Moreover, four channels in the left hemisphere near P3, P5, and F5 showed a robust increase as the working memory load increased from 1 to 3 items. Notably, the hemodynamic response did not asymptote at 1-2 items as expected from previous fMRI studies with adults. Finally, 4-year-olds showed a more robust parietal response relative to 3-year-olds, and an increasing sensitivity to the memory load manipulation. These results demonstrate that fNIRS is an effective tool to study the neural processes that underlie the early development of VWM capacity.
MeSH Terms
- Aging
- Brain
- Child Development
- Child, Preschool
- Data Interpretation, Statistical
- Female
- Form Perception
- Frontal Lobe
- Functional Laterality
- Functional Neuroimaging
- Hemoglobins
- Humans
- Image Processing, Computer-Assisted
- Male
- Memory, Short-Term
- Nerve Net
- Parietal Lobe
- Photic Stimulation
- Psychomotor Performance
- Spectroscopy, Near-Infrared
Keywords
- Development
- Functional neuroimaging
- Near-infrared spectroscopy
- Visual working memory
- Working memory capacity
Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two-stage genome-wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community-based studies. Genotypes for genome-wide single-nucleotide polymorphisms (SNPs) were imputed to approximately 2.5 million SNPs in HapMap and association with VTE assessed using study-design appropriate regression methods. Meta-analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (P ≤ 0.0016) from the discovery GWAS were tested for association in an additional 3,231 cases and 3,536 controls from three case-control studies. In the combined data from these two stages, additional genome-wide significant associations were observed on 4q35 at F11 (top SNP rs4253399, intronic to F11) and on 4q28 at FGG (rs6536024, 9.7 kb from FGG; P < 5.0 × 10(-13) for both). The associations at the FGG locus were not completely explained by previously reported variants. Loci at or near SUSD1 and OTUD7A showed borderline yet novel associations (P < 5.0 × 10(-6) ) and constitute new candidate genes. In conclusion, this large GWAS replicated key genetic associations in F5 and ABO, and confirmed the importance of F11 and FGG loci for VTE. Future studies are warranted to better characterize the associations with F11 and FGG and to replicate the new candidate associations.
MeSH Terms
- Aged
- Aging
- Case-Control Studies
- Cohort Studies
- Female
- Genome-Wide Association Study
- Humans
- Male
- Meta-Analysis as Topic
- Middle Aged
- Polymorphism, Single Nucleotide
- Regression Analysis
- Risk Factors
- Venous Thromboembolism
To investigate the association of pathogenic Escherichia coli fimbrial adhesins with the development of diarrhoea in piglets of different age groups and to test their relative competitiveness, piglets were orally inoculated with a mixture of E. coli strains harbouring F4, F5, F6, F18 and F41 fimbrial genes. A total of 537 E. coli strains with haemolytic activity were isolated from 36 diarrhoeic piglets. The F4 fimbrial gene was observed in 98.5%, 97.6% and 80.6% strains carrying fimbrial genes isolated from diarrhoeic piglets that were infected at 1, 3 and 5 weeks of age, respectively. These data demonstrate that F4 fimbriae are highly associated with diarrhoea in piglets of all age groups. Interestingly, the F18 fimbrial gene was observed in 2.4% and 25.4% strains carrying fimbrial genes isolated from the 3- and 5-week-old groups, respectively, which confirms that F18 fimbriae are associated with diarrhoea in piglets from late stages of suckling to post-weaning, and are more related to diarrhoea in weaned than in unweaned piglets.
MeSH Terms
- Aging
- Animals
- Animals, Suckling
- Diarrhea
- Enterotoxigenic Escherichia coli
- Escherichia coli Infections
- Fimbriae, Bacterial
- Gene Expression Regulation, Bacterial
- Swine
- Swine Diseases
The prevalence rate of insomnia among 424 married women and its associated factors were surveyed. Insomnia is defined as having one of the following symptoms one or more times per week: difficulty inducing sleep (Fl), difficulty maintaining sleep (F2), early morning awakening (F3), light sleep (F4), or worry about poor sleep quality (F5). Poor sleep as a whole in the past one month (F6) was also inquired about. Percentages of Fl, F2, F3 and F5 among the subjects in their sixties were 21.3%, 13.3%, 6.7% and 10.7%, respectively, relatively higher than those of subjects in their thirties or forties. There was a significant difference in the percentage of F6 among four age categories (p < 0.05), and the percentage of F6 was highest (23.3%) in those in their thirties. Depressive state correlated with six insomnia items, Fl to F6 (rs.=-0.195, -0.161, -0.117,-0.221, -0.176, 0.284, respectively). Perceived health status correlated with Fl (-0.237), F4 (-0.213), F5 (-0.259), and F6 (0.373). Present medical condition correlated with Fl (-0.195), F3 (-0.146), and F5 (-0.220). The prevalence rates of insomnia for subjects in their thirties, forties, fifties and sixties were 16.7%, 17.7%, 25.7%, and 24.0%, respectively. Increases in the percentages of difficulty in inducting and maintaining sleep, early morning awakening and worry about poor sleep quality in the subjects in their sixties, and sleep dissatisfaction of those in their thirties were recognized.
Keywords
- Aging
- Depressive state
- Field survey
- Insomnia
- Subjective sleep inventory
The ovaries are the primary targets of senescence effects in mammalian and avian species. In the present study, relationships between reproductive aging, sex steroids and the growth pattern of the pre-ovulatory follicle wall were investigated using young hens with long clutch (YLC), old hens with long clutch (OLC), old hens with short clutch (OSC), and old hens with interrupted long clutch (OILC). Experiment 1: Hens were sacrificed 1.5 and 14.5 h after ovulation. Experiment 2: YLC and OILC hens were sacrificed 3.5 h after treatments with LH and/or aminoglutethimide (AG), an inhibitor of steroid synthesis. Volumes of pre-ovulatory follicles (F1-F5) and plasma concentrations of ovarian steroids were determined. Experiment 3: Granulosa and theca cells from F3 follicles of OSC and/or YLC hens were exposed in vitro to estradiol-17beta (E2), testosterone (T) and LH and the proliferative activity of the cells was examined using CellTiter 96 Aqueous One Solution Assay. In YLC and OLC groups, the total volume of F1-F5 follicles rose between 1.5 and 14.5 h after ovulation (P < 0.01), negatively correlating with the plasma level of E2 (P < 0.01). There was no growth of pre-ovulatory follicles in the middle of the ovulatory cycle in the OSC group, with a positive correlation being present between E2 and the follicular volume (P < 0.05). In young hens, AG caused a rise in the total follicular volume. This rise was associated with a fall in E2 (r = -0.54, P < 0.05). E2 enhanced proliferation of granulosa cells from YLC and OSC groups. The proliferative activity of granulosa and theca cells of YLC hens depended on the interaction between T and LH (P < 0.01). These data indicate for the first time that the growth pattern of pre-ovulatory follicles during the ovulatory cycle changes in the course of reproductive aging. E2 seems to play a dual role in this adjustment; it stimulates the growth of the follicular wall in reproductive aged hens, whereas it may inhibit this process in young birds. T and LH are apparently involved in the growth regulation during the pre-ovulatory surge in young hens.
MeSH Terms
- Age Factors
- Aging
- Aminoglutethimide
- Animals
- Aromatase Inhibitors
- Cell Membrane
- Cell Proliferation
- Cells, Cultured
- Chickens
- Female
- Gonadal Steroid Hormones
- Granulosa Cells
- Injections
- Luteinizing Hormone
- Ovarian Follicle
- Reproduction
- Theca Cells
Catecholamines regulate glucose metabolism and affect hepatic glucose production mainly through beta2-adrenergic receptors. The hypothesis was tested that gene expression and numbers of hepatic beta-adrenergic receptors in calves are influenced by age. Examined developmental stages included pre-term (P0) and full-term (F0) calves immediately after birth, full-term calves on day 5 of life (F5), and veal calves (VC) at the age of 159 days. Expression of beta1-, beta2-, and beta3-adrenergic receptor mRNA was measured by real-time PCR. Receptor binding was quantified by saturation binding assays using (3H)-CGP-12177 as a ligand. Abundance of mRNA differed among beta-adrenergic subtypes (beta2 > beta1 > beta3; P < 0.01). Beta3-adrenergic receptor mRNA was undetectable in VC. mRNA abundance for beta2-adrenergic receptors was higher (P < 0.05) in VC than P0 and for beta3-adrenergic receptors was higher (P < 0.001) in F5 than P0. Binding studies revealed most binding of (3H)-CGP-12177 to beta2-adrenergic receptors, which were highest in VC (P < 0.001) and higher (P < 0.05) in F5 than P0. Binding sites correlated positively with mRNA levels of beta2-adrenergic receptors (r = 0.67; P < 0.001), with hepatic activities of phosphoenolpyruvate kinase (r = 0.73; P < 0.001) and with pyruvate kinase (r = 0.4; P < 0.05), and with plasma glucose concentrations (r = 0.5; P < 0.01). In conclusion, mRNA of all three beta-adrenergic receptor subtypes were found in liver, with beta2-adrenergic receptors being the dominant subtype. Numbers of beta2-adrenergic receptors increased with age and were mainly regulated at the transcriptional level. Numbers of beta-adrenergic receptors were positively associated with hepatic activities of gluconeogenetic enzymes and with plasma glucose levels, suggesting functional importance.
MeSH Terms
- Aging
- Animals
- Binding Sites
- Cattle
- Female
- Gluconeogenesis
- Glyceraldehyde-3-Phosphate Dehydrogenases
- Liver
- Male
- Phosphoenolpyruvate Carboxykinase (GTP)
- Polymerase Chain Reaction
- Pyruvate Carboxylase
- RNA, Messenger
- Receptors, Adrenergic, beta
- Receptors, Adrenergic, beta-1
- Receptors, Adrenergic, beta-2
- Receptors, Adrenergic, beta-3
Age associated thymic atrophy has been shown to be linked to problems with rearrangement of the beta chain of the T cell receptor (TCR) in male mice during the early phases of the intrathymic T cell developmental pathway. In this study, thymic atrophy in female mice was found to occur at a different rate than in male mice. At 9 months of age there was a significantly greater number of cells in the thymus of female mice compared with male mice, with the major difference found in the CD4 CD8 populations. The thymii of female mice at 9 months of age contained double the number of these cells compared with male mice. Analysis of the CD4 CD8 cells at 9 months of age demonstrated increased numbers of cells expressing higher levels of CD3 in females compared with males indicating that in females more of these cells were producing successful alphabetaTCR pairings. In F5 transgenic mice comparison of the CD4 CD8 population revealed no significant difference in their absolute numbers at 9 months of age. These results indicate that the gender differences at this time point were due to fewer permitted divisions prior to the expression of a selectable TCR alpha chain within the CD4 CD8 populations in male compared with female mice. This gender difference was not due to the action of testosterone and unlikely to be due to differences in the level of oestrogen. The potential mechanisms of this difference may be related to a regulatory feedback of peripheral T cells on the developing thymocyte populations. Such age related changes in the numbers of cells within distinct thymic subpopulations leads to the possibility that the potential repertoire in females is greater than in males later in life.
MeSH Terms
- Aging
- Animals
- Atrophy
- CD3 Complex
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Sex Characteristics
- T-Lymphocyte Subsets
- Thymus Gland
Involution of the thymus is a feature of age and precedes inefficient functioning of the immune system. C57BL/10 mice show an 83% reduction in number of thymocytes between 3 and 20 mo of age, with a significant decline in each of the thymic subsets defined by their expression of CD4 and CD8. The similar percentage contribution of each subset to the whole at 3, 12, and 20 mo suggests a lesion in the T cell developmental pathway within an early subset. The CD3- CD4- CD8- subset showed a significant decline in number by 20 mo of age, but despite this reduction, no significant difference was noted in the number of [[CD44]] CD25- cells, the earliest stage of this subset between 3 and 20 mo of age. A significant decline in the number of their progeny, the [[CD44]] CD25 , and the progeny of these cells, the [[CD44]]- CD25 cells, was noted by 12 mo of age. Expression of CD25 within this subset is associated with rearrangement of TCR beta-chain genes. F5 transgenic mice, carrying a complete TCR-alphabeta transgene under the control of a CD2 minigene cassette on a C57BL/10 background, showed no age-associated thymic atrophy in any of the defined thymic subsets over the same period as the normal C57BL/10 mice. Similar results were noted with mice carrying the same transgene but which in addition were also RAG-1-. The results indicate that age-associated thymic involution was associated with problems with rearrangement of the TCR beta-chain genes affecting the production of thymocytes.
MeSH Terms
- Aging
- Animals
- Atrophy
- CD3 Complex
- CD4 Antigens
- CD8 Antigens
- Cell Differentiation
- Crosses, Genetic
- Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
- Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
- Homeodomain Proteins
- Immunophenotyping
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Proteins
- Receptors, Antigen, T-Cell
- T-Lymphocyte Subsets
- Thymus Gland
Few studies have examined the effect of age on the ovulation cycle of the hen. Our aim was to determine if changes in the ovary account for the decrease in egg production with age. Young hens (28-38 wk of age) laying at least 20 eggs per sequence and old hens (53-63 wk of age) laying 3-6 eggs per sequence were used. We determined luteinizing hormone (LH) sensitivity of the ovary of young and old hens by measuring LH stimulable adenylyl cyclase (AC) activity of the granulosa layer. We also measured theca- and granulosa-layer weights and steroid concentrations of these layers and of the serum in young and old hens. Mean basal AC activity (pg/min/mg protein) for the largest (F1) and second largest (F2) follicles from young and old hens did not differ. A significant dose-response relationship to LH was present in all groups, and AC responsiveness to increasing doses of LH was greater in the F1 and F2 follicles of young hens than in the same follicles of old hens. The F4 and F5 follicles of young hens had a significantly greater estradiol (E2) concentration (pg/mg theca protein) compared to old hens, while the E2 concentration in the F2 follicle was greater in old hens. The theca layer of the F1 follicle of old hens weighed significantly more than that of young hens, whereas the theca layer of the F3, F4 and F5 follicles from young hens weighed more than those of old hens.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Adenylyl Cyclases
- Aging
- Animals
- Chickens
- Dose-Response Relationship, Drug
- Estradiol
- Female
- Granulosa Cells
- Luteinizing Hormone
- Organ Size
- Ovulation
- Progesterone
- Testosterone
- Theca Cells