F3

Версия от 18:34, 12 мая 2021; OdysseusBot (обсуждение | вклад) (Новая страница: «Tissue factor precursor (TF) (Coagulation factor III) (Thromboplastin) (CD142 antigen) ==Publications== {{medline-entry |title=A Comprehensive Analysis of Age a...»)
(разн.) ← Предыдущая версия | Текущая версия (разн.) | Следующая версия → (разн.)

Tissue factor precursor (TF) (Coagulation factor III) (Thromboplastin) (CD142 antigen)

PublicationsПравить

A Comprehensive Analysis of Age and Gender Effects in European Portuguese Oral Vowels.

The knowledge about the age effects in speech acoustics is still disperse and incomplete. This study extends the analyses of the effects of age and gender on acoustics of European Portuguese (EP) oral vowels, in order to complement initial studies with limited sets of acoustic parameters, and to further investigate unclear or inconsistent results. A database of EP vowels produced by a group of 113 adults, aged between 35 and 97, was used. Duration, fundamental frequency (f0), formant frequencies (F1 to F3), and a selection of vowel space metrics (F1 and F2 range ratios, vowel articulation index [VAI] and formant centralization ratio [FCR]) were analyzed. To avoid the arguable division into age groups, the analyses considered age as a continuous variable. The most relevant age-related results included: vowel duration increase in both genders; a general tendency to formant frequencies decrease for females; changes that were consistent with vowel centralization for males, confirmed by the vowel space acoustic indexes; and no evidence of F3 decrease with age, in both genders. This study has contributed to knowledge on aging speech, providing new information for an additional language. The results corroborated that acoustic characteristics of speech change with age and present different patterns between genders.


Keywords

  • Acoustic
  • Aging voice
  • European Portuguese
  • Oral vowel


Prenatal exposure to an environmentally relevant phthalate mixture accelerates biomarkers of reproductive aging in a multiple and transgenerational manner in female mice.

Phthalates are known endocrine-disrupting chemicals that are found in many consumer products. Our laboratory previously developed a relevant phthalate mixture consisting of six phthalates and found that it disrupted female fertility in mice. However, it is unknown if prenatal exposure to phthalate mixtures can accelerate reproductive aging and if this occurs in multiple generations. Thus, we tested the hypothesis that prenatal exposure to a mixture of phthalates accelerates biomarkers of reproductive aging in multiple generations of female mice. Pregnant CD-1 mice were orally dosed with vehicle control or a phthalate mixture (20 μg/kg/day-500 mg/kg/day) daily from gestational day 10 to birth. Adult F1 females born to these dams were used to create the F2 and F3 generations by mating them with unexposed males. At 13 months, estrous cyclicity was monitored and ovaries and sera were collected for analysis. In the F1 generation, the mixture decreased testosterone and inhibin B levels, but increased follicle-stimulating hormone and luteinizing hormone levels compared to control. In the F2 generation, the phthalate mixture decreased the percent of antral follicles and testosterone hormone levels compared to control. In the F3 generation, prenatal exposure to the phthalate mixture increased ovarian weight, increased the time in metestrus/diestrus, altered follicle numbers, and decreased the levels of luteinizing hormone compared to control. Collectively, these data suggest that prenatal exposure to a phthalate mixture may accelerate several biomarkers of reproductive aging in a multi- and transgenerational manner in female mice.


Keywords

  • cyclicity
  • hormone
  • mixture
  • ovary
  • phthalates
  • reproductive aging
  • transgenerational


Combining Frontal Transcranial Direct Current Stimulation With Walking Rehabilitation to Enhance Mobility and Executive Function: A Pilot Clinical Trial.

This pilot study assessed whether frontal lobe transcranial direct current stimulation (tDCS) combined with complex walking rehabilitation is feasible, safe, and shows preliminary efficacy for improving walking and executive function. Participants were randomized to one of the following 18-session interventions: active tDCS and rehabilitation with complex walking tasks (Active/Complex); sham tDCS and rehabilitation with complex walking tasks (Sham/Complex); or sham tDCS and rehabilitation with typical walking (Sham/Typical). Active tDCS was delivered over F3 (cathode) and F4 (anode) scalp locations for 20 min at 2 mA intensity. Outcome measures included tests of walking function, executive function, and prefrontal activity measured by functional near infrared spectroscopy. Ninety percent of participants completed the intervention protocol successfully. tDCS side effects of tingling or burning sensations were low (average rating less than two out of 10). All groups demonstrated gains in walking performance based on within-group effect sizes (d ≥ 0.50) for one or more assessments. The Sham/Typical group showed the greatest gains for walking based on between-group effect sizes. For executive function, the Active/Complex group showed the greatest gains based on moderate to large between-group effect sizes (d = 0.52-1.11). Functional near-infrared spectroscopy (fNIRS) findings suggest improved prefrontal cortical activity during walking. Eighteen sessions of walking rehabilitation combined with tDCS is a feasible and safe intervention for older adults. Preliminary effects size data indicate a potential improvement in executive function by adding frontal tDCS to walking rehabilitation. This study justifies future larger clinical trials to better understand the benefits of combining tDCS with walking rehabilitation.


Keywords

  • Aging
  • cognition
  • rehabilitation
  • transcranial direct current stimulation
  • walking


Assessing the Retest Reliability of Prefrontal EEG Markers of Brain Rhythm Slowing in the Eyes-Closed Resting State.

[i]Objective[/i]. We examined whether prefrontal lobe EEG markers of slower brain rhythms, which are correlated with functional brain aging, can reliably reflect those of other brain lobes, as measured by a multichannel device. [i]Methods[/i]. EEG measurements were taken of 112 healthy individuals aged 20 to 69 years in the eyes-closed resting state. A 5-minute measurement was taken at 8 regions (Fp1, Fp2, F3, F4, T3, T4, O1, O2). Indices (median frequency [MDF], peak frequency [PF]) that quantitatively reflect the characteristics of EEG slowing, and traditional commonly used spectral indices (absolute powers as delta, theta, alpha, beta, and relative power as alpha-to-theta ratio [[[ATR]]]), were extracted from the EEG signals. For these indices, the differences between the prefrontal lobe and other areas were analyzed and the test-retest reproducibility was investigated. [i]Results[/i]. The EEG slowing indicators showed high conformity over all brain lobes and stable reproducibility. On the other hand, the typical EEG spectral indicators delta, theta, alpha, beta, and ATR differed between brain regions. [i]Conclusion[/i]. It was found that EEG slowing markers, which were used for assessing the aging or degeneration of brain functions, could be reliably extracted from a prefrontal EEG alone. [i]Significance[/i]. These findings suggest that EEG prefrontal markers may reflect markers of other brain regions when a multi-channel device is used. Thus, this method may constitute a low-cost, wearable, wireless, easily accessible, and noninvasive tool for neurological assessment that could be used in the early detection of cognitive decline and in the prevention of dementia.


Keywords

  • EEG
  • EEG slowing
  • brain aging
  • dominant frequency
  • prefrontal


Multigenerational exposure to TiO nanoparticles in soil stimulates stress resistance and longevity of survived C. elegans via activating insulin/IGF-like signaling.

With increasing release of nanoparticles (NPs) into the environment, soil organisms likely suffer from high dose and long duration of NPs contamination, while the effect of NPs across multiple generations in soil is rarely studied. Herein, we investigated how multigenerational exposure to different crystal forms (anatase, rutile, and their mixture) of TiO NPs (nTiO ) affected the survival, behavior, physiological and biochemical traits, and lifespan of nematodes (C. elegans) in a paddy soil. The soil property changed very slightly after being spiked with nTiO , and the toxicities of three nTiO forms were largely comparable. The nTiO exposure adversely influenced the survival and locomotion of nematodes, and increased intracellular reactive oxygen species (ROS) generation. Interestingly, the toxic effect gradually attenuated and the lifespan of survived nematodes increased from the P0 to F3 generation, which was ascribed to the survivor selection and stimulatory effect. The lethal effect and the increased oxidative stress may continuously screen out offspring possessing stronger anti-stress capabilities. Moreover, key genes (daf-2, age-1, and skn-1) in the insulin/IGF-like signaling (IIS) pathway actively responded to the nTiO exposure, which further optimized the selective expression of downstream genes, increased the antioxidant enzyme activities and antioxidant contents, and thereby increased the stress resistance and longevity of survived nematodes across successive generations. Our findings highlight the crucial role of bio-responses in the progressively decreased toxicity of nTiO , and add new knowledge on the long-term impact of soil nTiO contamination.

MeSH Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Insulin
  • Longevity
  • Nanoparticles
  • Oxidative Stress
  • Soil
  • Titanium

Keywords

  • Insulin/IGF-like signaling
  • Longevity
  • Multigenerational toxicity
  • Nanomaterial
  • Soil nematode


Co-expression network analysis identified hub genes critical to triglyceride and free fatty acid metabolism as key regulators of age-related vascular dysfunction in mice.

Aging has often been linked to age-related vascular disorders. The elucidation of the putative genes and pathways underlying vascular aging likely provides useful insights into vascular diseases at advanced ages. Transcriptional regulatory network analysis is the key to describing genetic interactions between molecular regulators and their target gene transcriptionally changed during vascular aging. A total of 469 differentially expressed genes were parsed into 6 modules. Among the incorporated sample traits, the most significant module related to vascular aging was associated with triglyceride and enriched with biological terms like proteolysis, blood circulation, and circulatory system process. The module associated with triglyceride was preserved in an independent microarray dataset, indicating the robustness of the identified vascular aging-related subnetwork. Additionally, Enpp5, Fez1, Kif1a, F3, H2-Q7, and their interacting miRNAs mmu-miR-449a, mmu-miR-449c, mmu-miR-34c, mmu-miR-34b-5p, mmu-miR-15a, and mmu-let-7, exhibited the most connectivity with external lipid-related traits. Transcriptional alterations of the hub genes Enpp5, Fez1, Kif1a, and F3, and the interacting microRNAs mmu-miR-34c, mmu-miR-34b-5p, mmu-let-7, mmu-miR-449a, and mmu-miR-449c were confirmed. Our findings demonstrate that triglyceride and free fatty acid-related genes are key regulators of age-related vascular dysfunction in mice and show that the hub genes for Enpp5, Fez1, Kif1a, and F3 as well as their interacting miRNAs mmu-miR-34c, mmu-miR-34b-5p, mmu-let-7, mmu-miR-449a, and mmu-miR-449c, could serve as potential biomarkers in vascular aging. The microarray gene expression profiles of aorta samples from 6-month old mice (n=6) and 20-month old mice (n=6) were processed to identify nominal differentially expressed genes. These nominal differentially expressed genes were subjected to a weighted gene co-expression network analysis. A network-driven integrative analysis with microRNAs and transcription factors was performed to define significant modules and underlying regulatory pathways associated with vascular aging, and module preservation test was conducted to validate the age-related modules based on an independent microarray gene expression dataset in mice aorta samples including three 32-week old wild-type mice (around 6-month old) and three 78-week old wild-type mice (around 20-month old). Gene ontology and protein-protein interaction analyses were conducted to determine the hub genes as potential biomarkers in the progress of vascular aging. The hub genes were further validated with quantitative real-time polymerase chain reaction in aorta samples from 20 young (6-month old) mice and 20 old (20-month old) mice.

MeSH Terms

  • Aging
  • Animals
  • Fatty Acids, Nonesterified
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Lipid Metabolism
  • Mice
  • Microarray Analysis
  • Signal Transduction
  • Triglycerides
  • Vascular Diseases

Keywords

  • aging
  • co-expression network
  • hub gene
  • module
  • mouse
  • vascular dysfunction


Transgenerational Effects of Extended Dauer Diapause on Starvation Survival and Gene Expression Plasticity in [i]Caenorhabditis elegans[/i].

Phenotypic plasticity is facilitated by epigenetic regulation, and remnants of such regulation may persist after plasticity-inducing cues are gone. However, the relationship between plasticity and transgenerational epigenetic memory is not understood. Dauer diapause in [i]Caenorhabditis elegans[/i] provides an opportunity to determine how a plastic response to the early-life environment affects traits later in life and in subsequent generations. We report that, after extended diapause, postdauer worms initially exhibit reduced reproductive success and greater interindividual variation. In contrast, F3 progeny of postdauers display increased starvation resistance and lifespan, revealing potentially adaptive transgenerational effects. Transgenerational effects are dependent on the duration of diapause, indicating an effect of extended starvation. In agreement, RNA-seq demonstrates a transgenerational effect on nutrient-responsive genes. Further, postdauer F3 progeny exhibit reduced gene expression plasticity, suggesting a trade-off between plasticity and epigenetic memory. This work reveals complex effects of nutrient stress over different time scales in an animal that evolved to thrive in feast and famine.

MeSH Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Cell Plasticity
  • Cohort Effect
  • Diapause
  • Epigenesis, Genetic
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Larva
  • Longevity
  • Signal Transduction
  • Starvation

Keywords

  • dauer
  • diapause
  • epigenetic
  • plasticity
  • starvation
  • transgenerational


Influence of Supplemental Protein on the Life Expectancy and Reproduction of the Chinese Citrus Fruit Fly, Bactrocera minax (Enderlein) (Tetradacus minax) (Diptera: Tephritidae).

Bactrocera minax (Enderlein) (Diptera: Tephritidae) is a major citrus pest in China, whose artificial rearing technology of the adult is not well documented to date. In this study, we tried to determine if supplementing proteins to the adult diet could result in the enhancement of some fitness parameters of B. minax. Four feeds with varying protein source were provided as F0 (water), F1 (sucrose), F2 (sucrose yeast), and F3 (sucrose peptone). F0 and F1 being the control, F2 and F3 were protein food types. The results showed that adults fed by F2 and F3 lived longer with 40.1 d and 32.8 d, respectively, had reduced death rates (death peaks were delayed for 5.6 d and 4.1 d, respectively), increased mating frequencies (8.1 and 5.3 per females, 4.7 and 7.3 per males, respectively), and longer mating durations (with 42 d and 34 d). In addition, females recorded an increased adult ovary development, more egg load (with 94.8 and 77.3 brood eggs per ovary) and to greater oviposition rates of 63.2 eggs/female and 19.3 eggs/female. Based on our results, protein supplements enhanced B. minax survival, mating, and fecundity. This study does not only provide basic knowledge to implement artificial rearing of B. minax, but also deepens our understanding on its physiology that could be used to enhance the management of the pest.

MeSH Terms

  • Animals
  • Dietary Proteins
  • Dietary Supplements
  • Female
  • Fertility
  • Longevity
  • Male
  • Oviposition
  • Sexual Behavior, Animal
  • Tephritidae


Early-life exposure to three size-fractionated ultrafine and fine atmospheric particulates in Beijing exacerbates asthma development in mature mice.

Epidemiological studies have suggested that elevated levels of air pollution contribute to an increased incidence or severity of asthma. Although late-onset adult asthma seems to be more attributable to environmental risk factors, limited data is available on the impact of early-life exposure to size-fractionated ambient particulate matter (PM) on asthma in adults. We aimed to determine the effect on the development and exacerbation of asthma in the adult after the mice were exposed as juveniles to three size-fractionated ambient particulates collected from Beijing. The three size-fractionated ambient particulates were collected from urban Beijing in winter, heavily affected by traffic and coal-fired emissions. The typical morphological and major chemical components of the PM were characterized first. Oxidative stress and expression of DNA methyltransferases (DNMTs) were then examined in vitro and in the lungs of mouse pups 48 h after exposure to PM by oropharyngeal aspiration. When the exposed and control juvenile mice matured to adulthood, an antigen-induced asthma model was established and relevant bio-indices were assessed. PM with different granularities can induce oxidative stress; in particular, F1, with the smallest size (< 0.49 μm), decreased the mRNA expression of DNMTs in vitro and in vivo the most significantly. In an asthma model of adult mice, previous exposure as juveniles to size-fractionated PM caused increased peribronchiolar inflammation, increased airway mucus secretion, and increased production of Th2 cytokines and chemokines. In general, F1 and F2 (aerodynamic diameter < 0.95 μm) particulates affected murine adult asthma development more seriously than F3 (0.95-1.5 μm). Moreover, F1 led to airway inflammation in the form of both increased neutrophils and eosinophils in BALF. The activation of the TGF-β1/Smad2 and Smad3/Stat3 signaling pathways leading to airway fibrosis was more profoundly induced by F1. This study demonstrated that exposure to ambient PM in juvenile mice enhanced adult asthma development, as shown by increased Th2 responses, which might be associated with the persistent effects resulting from the oxidative stress and decreased gene expression of DNMTs induced by PM exposure. The observed differences between the effects of three size-fractionated particulates were attributed to particle sizes and chemical constituents, including heavy metals and also PAHs, since the amounts of PAH associated with more severe toxicity were enriched equivalently in the F1 and F2 fractions. Relative to the often mentioned PM2.5, PM with an aerodynamic diameter smaller than 0.95 μm had a more aggravating effect on asthma development.

MeSH Terms

  • Aging
  • Air Pollutants
  • Animals
  • Asthma
  • Beijing
  • Bronchoalveolar Lavage Fluid
  • Cell Line
  • Cytokines
  • Female
  • Immunoglobulins
  • Inhalation Exposure
  • Lung
  • Mice, Inbred BALB C
  • Oxidative Stress
  • Particle Size
  • Particulate Matter

Keywords

  • Adulthood
  • Allergic asthma
  • Early-life exposure
  • Particulate matter


Multigenerational effects of 4-methylbenzylidene camphor (4-MBC) on the survival, development and reproduction of the marine copepod Tigriopus japonicus.

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


Effects of Aging on Vocal Fundamental Frequency and Vowel Formants in Men and Women.

This study reports data on vocal fundamental frequency (f ) and the first four formant frequencies (F1, F2, F3, F4) for four vowels produced by speakers in three adult age cohorts, in a test of the null hypothesis that there are no age-related changes in these variables. Participants were 43 men and 53 women between the ages of 20 and 92 years. The most consistent age-related effect was a decrease in f for women. Significant differences in F1, F2, and F3 were vowel-specific for both sexes. No significant differences were observed for the highest formant F4. Women experience a significant decrease in f , which is likely related to menopause. Formant frequencies of the corner vowels change little across several decades of adult life, either because physiological aging has small effects on these variables or because individuals compensate for age-related changes in anatomy and physiology.

MeSH Terms

  • Acoustics
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Female
  • Humans
  • Male
  • Menopause
  • Middle Aged
  • Sex Factors
  • Sound Spectrography
  • Speech Acoustics
  • Speech Production Measurement
  • Voice Quality
  • Young Adult

Keywords

  • Adult acoustics
  • Aging voice
  • Formants
  • Fundamental frequency
  • Sex differences


Shedding light on gray(ing) areas: Connectivity and task switching dynamics in aging.

Control-demanding tasks rely on communication among regions of the frontoparietal network, areas that undergo significant age-related decline. Here, we integrate data from brain anatomy, electrophysiology (ERPs), and optical imaging (event-related optical signals, EROS) to characterize the spatial and temporal dynamics of preparatory control processes in middle to old age. Older adults participated in an experiment that required switching between a position and a meaning task (spatial Stroop), a paradigm that has been shown to primarily recruit prefrontal cortex in opposite hemispheres and is thought to involve the corpus callosum (CC). In middle-aged participants, switch trials resulted in greater negativity over F3 early in the preparatory period. Across the whole older adult sample, this switch-related frontal negativity was correlated with reaction time (RT) switch costs and EROS switch-related upregulation in the left middle frontal gyrus (MFG). Anterior CC volume was not directly correlated with switch costs, although CC volume predicted task-dependent coupling of left MFG and right MFG. Crucially, left MFG-seeded lagged cross-correlations revealed task-dependent connectivity; in the right-hemisphere-dependent position task, the timing and strength of switch-related coupling between left MFG and right MFG significantly predicted RT switch costs, even after controlling for age, CC volume, and the F3 switch effect. Together, these results suggest that a strong functional connectivity, likely hinged on the integrity of the underlying structural connections, is critical to being able to meet the demands of shifting processing across hemispheres, and that difficulty engaging such control dynamics leads to suboptimal performance.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Cerebral Cortex
  • Electroencephalography
  • Executive Function
  • Female
  • Frontal Lobe
  • Functional Laterality
  • Humans
  • Male
  • Middle Aged
  • Neural Pathways
  • Parietal Lobe
  • Reaction Time
  • Stroop Test

Keywords

  • ERPs
  • cognitive aging
  • cognitive control
  • corpus callosum
  • event-related optical signal
  • functional connectivity
  • task switching


Chronic exposure of zinc oxide nanoparticles causes deviant phenotype in Drosophila melanogaster.

Zinc oxide nanoparticles (ZnO NPs) are commonly used nanomaterials (NMs) with versatile applications from high-end technologies to household products. This pervasive utilisation has brought human in the close interface with nanoparticles (NPs), hence questioning their safety prior to usage is a must. In this study, we have assessed the effects of chronic exposure to ZnO NPs (<50nm) on the model organism Drosophila melanogaster. Potential toxic effects were studied by evaluating longevity, climbing ability, oxidative stress and DNA fragmentation. Ensuing exposure, the F0 (parent), F1, F2, F3 and F4 generation flies were screened for the aberrant phenotype. Flies exposed to ZnO NPs showed distinctive phenotypic changes, like deformed segmented thorax and single or deformed wing, which were transmitted to the offspring's in subsequent generations. The unique abnormal phenotype is evident of chronic toxicity induced by ZnO NPs, although appalling, it strongly emphasize the importance to understand NPs toxicity for safer use.

MeSH Terms

  • Abnormalities, Drug-Induced
  • Animals
  • DNA Damage
  • DNA Fragmentation
  • Drosophila melanogaster
  • Hemocytes
  • Longevity
  • Metal Nanoparticles
  • Motor Activity
  • Mutagens
  • Oxidative Stress
  • Phenotype
  • Risk Assessment
  • Zinc Oxide

Keywords

  • Drosophila melanogaster
  • Genotoxicity
  • Nanotoxicology
  • Risk assessment
  • Zinc oxide nanoparticles


Treatment of Chronic Hepatitis C in the Aged - Does It Impact Life Expectancy? A Decision Analysis.

Recent studies have demonstrated that the efficacy of interferon-free direct-acting antiviral agents (DAAs) in patients over 70 is similar to that of younger age groups. Evidence continues to mount that life expectancy (LE) increases with successful treatment of hepatitis C (HCV) patients with advanced fibrosis. The evidence in older people is more limited. Our aim was to estimate the life year (LY) and quality-adjusted life year (QALY) gained by treatment of naïve patients with HCV as a function of patient's age and fibrosis stage. We constructed a Markov model of HCV progression toward advanced liver disease. The primary outcome was LY and QALY saved. The model and the sustained virological response of HCV infected subjects treated with a fixed-dose combination of the NS5B polymerase inhibitor Sofosbuvir and the NS5A replication complex inhibitor Ledipasvir were based on the published literature and expert opinion. Generally, both the number of LY gained and QALY gained gradually decreased with advancing age but the rate of decline was slower with more advanced fibrosis stage. For patients with fibrosis stage F1, F2 and F3, LY gained dropped below six months if treated by the age of 55, 65 or 70 years, respectively, while for a patient with fibrosis stage F4, the gain was one LY if treated by the age of 75. The QALY gained for treated over untreated elderly were reasonably high even for those treated at early fibrosis stage. There is a significant life expectancy benefit to HCV treatment in patients up to age 75 with advanced-stage fibrosis.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents
  • Benzimidazoles
  • Decision Support Techniques
  • Disease Progression
  • Female
  • Fluorenes
  • Hepatitis C, Chronic
  • Humans
  • Life Expectancy
  • Male
  • Markov Chains
  • Middle Aged
  • Quality-Adjusted Life Years
  • Sofosbuvir
  • Uridine Monophosphate


Transgenerational programming of longevity and reproduction by post-eclosion dietary manipulation in Drosophila.

Accumulating evidence suggests that early-life diet may program one's health status by causing permanent alternations in specific organs, tissues, or metabolic or homeostatic pathways, and such programming effects may propagate across generations through heritable epigenetic modifications. However, it remains uninvestigated whether postnatal dietary changes may program longevity across generations. To address this question of important biological and public health implications, newly-born flies (F0) were collected and subjected to various post-eclosion dietary manipulations (PDMs) with different protein-carbohydrate (i.e., LP, IP or HP for low-, intermediate- or high-protein) contents or a control diet (CD). Longevity and fecundity analyses were performed with these treated F0 flies and their F1, F2 and F3 offspring, while maintained on CD at all times. The LP and HP PDMs shortened longevity, while the IP PDM extended longevity significantly up to the F3 generation. Furthermore, the LP reduced while the IP PDM increased lifetime fecundity across the F0-F2 generations. Our observations establish the first animal model for studying transgenerational inheritance of nutritional programming of longevity, making it possible to investigate the underlying epigenetic mechanisms and identify gene targets for drug discovery in future studies.

MeSH Terms

  • Animals
  • Diet
  • Dietary Carbohydrates
  • Dietary Proteins
  • Drosophila melanogaster
  • Epigenesis, Genetic
  • Female
  • Longevity
  • Male
  • Reproduction

Keywords

  • diet
  • longevity
  • nutritional programming
  • reproduction
  • transgenerational inheritance


Spectrographic Acoustic Vocal Characteristics of Elderly Women Engaged in Aerobics.

This study was carried out to characterize the voice of the elderly women engaged in aerobics through spectrographic analysis. The vocal emission /a:/ of 58 elderly women engaged in aerobics for the spectrographic analysis of broadband (BBS) and narrowband (NBS) was collected, through the Real-Time Spectrogram of KayPENTAX program, that provides information about the glottal source, the position of the vocal tract and the characteristics of vowels and consonants. ANOVA (Análise de Variância) test was used for associations and Pearson correlation test with a significance level of 5%. To the BBS, the elderly women had medium intensity of the tracing color of the formants (Fs), low presence of noise, and medium definition of F1 and F2. There was a medium defining F3 and F4 and regularity for age 60 years, medium definition F4 and high regularity of the tracing for 70 years, and medium definition of F3 and F4 and regularity of the tracing for 80 years. For the NBS, the elderly women had medium intensity of tracing color, little presence of noise, harmonic substitutions by noise and subharmonic; 60 and 80 years had medium definition of harmonics and regularity of tracing and high definition; and regular for 70 years. For 70 and 80 years, there was a presence of harmonics and medium presence for 60 years. There was a negative correlation between F2 and the group of 60 years and F3 with the general age. Even with myofunctional, structural, and functional changes of the larynx caused by advancing age, which may affect the vocal characteristics, the elderly women of this study showed few changes in tracing spectrogram.

MeSH Terms

  • Acoustics
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Cross-Sectional Studies
  • Exercise
  • Female
  • Glottis
  • Humans
  • Middle Aged
  • Phonation
  • Sex Factors
  • Sound Spectrography
  • Speech Acoustics
  • Speech Production Measurement
  • Vocal Cords
  • Voice Quality

Keywords

  • Aging
  • Elderly
  • Gymnastics
  • Spectrography
  • Voice
  • Voice disorders


Fat and carbohydrate intake over three generations modify growth, metabolism and cardiovascular phenotype in female mice in an age-related manner.

Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w) throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456) in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing.

MeSH Terms

  • Aging
  • Animals
  • Diet, High-Fat
  • Dietary Carbohydrates
  • Eating
  • Female
  • Heart
  • Humans
  • Lactation
  • Liver
  • Mice
  • Physiological Phenomena
  • Pregnancy
  • Prenatal Exposure Delayed Effects


Effect of semolina-jaggery diet on survival and development of Drosophila melanogaster.

Drosophila melanogaster is an ideal model organism for developmental studies. This study tests the potential of semolina-jaggery (SJ) diet as a new formulation for bulk rearing of flies. Semolina and jaggery are organic products obtained from wheat endosperm and cane sugar, respectively. Semolina is a rich source of carbohydrates and protein. Jaggery has a high content of dietary sugars. Moreover, preparation of semolina jaggery diet is cost-effective and easy. Thus, the current study aimed to compare survival and developmental parameters of flies fed the SJ diet to flies fed the standard cornmeal-sugar-yeast (CSY) diet. SJ diet enhanced survival of flies without affecting fecundity; male flies showed increased resistance to starvation. A higher number of flies emerged at F2 and F3 generation when fed the SJ diet than when fed the control CSY diet. SJ diet did not increase fly body weight and lipid percentage. Therefore, SJ diet can be used for bulk rearing of healthy flies at par with the standard cornmeal-sugar-yeast diet.

MeSH Terms

  • Animal Feed
  • Animals
  • Body Weight
  • Diet
  • Drosophila melanogaster
  • Female
  • Fertility
  • Food Deprivation
  • Larva
  • Lipids
  • Longevity
  • Male
  • Plant Extracts
  • Triticum

Keywords

  • Drosophila melanogaster
  • bulk rearing
  • longevity
  • semolina-jaggery diet


Docosahexaenoic acid in Arctic charr (Salvelinus alpinus): the importance of dietary supply and physiological response during the entire growth period.

The aim of this 14-month feeding study was to investigate the effects of dietary docosahexaenoic acid (DHA) on tissue fatty acid composition, DHA retention, and DHA content per biomass accrual in muscle tissues of Arctic charr (Salvelinus alpinus). A control feed, formulated with a relatively high DHA inclusion level (F1), was compared with feeds containing gradually reduced amounts of DHA (Feeds F2, F3, and F4). Arctic charr were randomly distributed among 12 tanks and fed one of the feeds in triplicate. The DHA content within muscle tissues of fish fed diets F1 and F2 was generally higher compared to fish fed diets F3 and F4. However, there was an interaction between dietary DHA treatment and season, which resulted in fish muscle tissues having similar DHA contents irrespective of dietary supply during specific sampling periods. Although diets F3 and F4 contained ~4-fold less DHA compared to diets F1 and F2, the retention of DHA in dorsal and ventral muscle tissue was up to 5-fold higher relative to the diet content in fish fed diets F3 and F4. However, the difference among treatments was dependent on the month sampled. In addition, younger fish retained DHA more efficiently compared to older fish. DHA (μg DHA/g/day) accrual in muscle tissue was independent of somatic growth, and there was no difference among treatments. The results suggested that dietary DHA may be essential throughout the life cycle of Arctic charr and that the DHA content of muscle tissues was influenced by diet and metabolic/physiological factors, such as specific DHA retention during the entire growth cycle . Finally, this long-term feeding study in Arctic charr indicated a non-linear function in DHA retention in dorsal and ventral muscle tissues throughout the life cycle, which varied in its relationship to dietary DHA.

MeSH Terms

  • Aging
  • Animals
  • Diet
  • Docosahexaenoic Acids
  • Fatty Acids
  • Muscles
  • Random Allocation
  • Trout

Keywords

  • Aquaculture
  • DHA
  • Nutrition
  • Retention


Starvation-induced transgenerational inheritance of small RNAs in C. elegans.

Evidence from animal studies and human famines suggests that starvation may affect the health of the progeny of famished individuals. However, it is not clear whether starvation affects only immediate offspring or has lasting effects; it is also unclear how such epigenetic information is inherited. Small RNA-induced gene silencing can persist over several generations via transgenerationally inherited small RNA molecules in C. elegans, but all known transgenerational silencing responses are directed against foreign DNA introduced into the organism. We found that starvation-induced developmental arrest, a natural and drastic environmental change, leads to the generation of small RNAs that are inherited through at least three consecutive generations. These small, endogenous, transgenerationally transmitted RNAs target genes with roles in nutrition. We defined genes that are essential for this multigenerational effect. Moreover, we show that the F3 offspring of starved animals show an increased lifespan, corroborating the notion of a transgenerational memory of past conditions.

MeSH Terms

  • Animals
  • Caenorhabditis elegans
  • Epigenesis, Genetic
  • Humans
  • Longevity
  • Models, Animal
  • RNA Interference
  • RNA, Helminth
  • RNA, Small Untranslated
  • Starvation


Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis.

The mechanisms by which air pollution has multiple systemic effects in humans are not fully elucidated, but appear to include inflammation and thrombosis. This study examines whether concentrations of ozone and components of fine particle mass are associated with changes in methylation on tissue factor (F3), interferon gamma (IFN-γ), interleukin 6 (IL-6), toll-like receptor 2 (TLR-2), and intercellular adhesion molecule 1 (ICAM-1). We investigated associations between air pollution exposure and gene-specific methylation in 777 elderly men participating in the Normative Aging Study (1999-2009). We repeatedly measured methylation at multiple CpG sites within each gene's promoter region and calculated the mean of the position-specific measurements. We examined intermediate-term associations between primary and secondary air pollutants and mean methylation and methylation at each position with distributed-lag models. Increase in air pollutants concentrations was significantly associated with F3, ICAM-1, and TLR-2 hypomethylation, and IFN-γ and IL-6 hypermethylation. An interquartile range increase in black carbon concentration averaged over the four weeks prior to assessment was associated with a 12% reduction in F3 methylation (95% CI: -17% to -6%). For some genes, the change in methylation was observed only at specific locations within the promoter region. DNA methylation may reflect biological impact of air pollution. We found some significant mediated effects of black carbon on fibrinogen through a decrease in F3 methylation, and of sulfate and ozone on ICAM-1 protein through a decrease in ICAM-1 methylation.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Air Pollutants
  • Air Pollution
  • CpG Islands
  • DNA Methylation
  • Humans
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma
  • Interleukin-6
  • Male
  • Middle Aged
  • Promoter Regions, Genetic
  • Thromboplastin
  • Toll-Like Receptor 2

Keywords

  • air pollution
  • effect modification
  • elderly
  • gene-specific DNA methylation
  • mediation analysis
  • traffic


Age differences in the association of obstructive sleep apnea risk with cognition and quality of life.

Using a sample of 2925 stroke-free participants drawn from a national population-based study, we examined cross-sectional associations of obstructive sleep apnea (OSA) risk with cognition and quality of life and whether these vary with age, while controlling for demographics and comorbidities. Included participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were aged 47-93 years. OSA risk was categorized as high or low based on responses to the Berlin Sleep Questionnaire. Cognitive function was assessed with standardized fluency and recall measures. Depressive symptoms were assessed with the four-item Center for Epidemiologic Studies Depression Scale. Health-related quality of life (HRQoL) was assessed with the Medical Outcomes Study Short Form-12 (SF-12). Multivariate analyses of covariance (mancova) statistics were applied separately to the cognitive and quality of life dependent variables while accounting for potential confounders (demographics, comorbidities). In fully adjusted models, those at high risk for OSA had significantly lower cognitive scores (Wilks' lambda = 0.996, F3,2786  = 3.31, P < 0.05) and lower quality of life [depressive symptoms and HRQoL] (Wilks' lambda = 0.989, F3,2786  = 10.02, P < 0.0001). However, some of the associations were age-dependent. Differences in cognition and quality of life between those at high and low obstructive sleep apnea risk were most pronounced during middle age, with attenuated effects after age 70 years.

MeSH Terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Cognition
  • Comorbidity
  • Cross-Sectional Studies
  • Depression
  • Diabetes Mellitus
  • Dyslipidemias
  • Female
  • Humans
  • Male
  • Middle Aged
  • Quality of Life
  • Risk Assessment
  • Sleep Apnea, Obstructive
  • Southeastern United States
  • Surveys and Questionnaires

Keywords

  • Berlin Sleep Questionnaire
  • age differences
  • cognitive function
  • depression
  • health-related quality of life
  • obstructive sleep apnea


Improvement of cognitive function and physical activity of aging mice by human neural stem cells over-expressing choline acetyltransferase.

Aging is characterized by progressive loss of cognitive and memory functions as well as decrease in physical activities. In the present study, a human neural stem cell line (F3 NSC) over-expressing choline acetyltransferase (F3.ChAT), an enzyme responsible for acetylcholine synthesis, was generated and transplanted in the brain of 18-month-old male ICR mice. Four weeks post-transplantation, neurobehavioral functions, expression of ChAT enzyme, production of acetylcholine and neurotrophic factors, and expression of cholinergic nervous system markers in transplanted animals were investigated. F3.ChAT NSCs markedly improved both the cognitive function and physical activity of aging animals, in parallel with the elevation of brain acetylcholine level. Transplanted F3 and F3.ChAT cells were found to differentiate into neurons and astrocytes, and to produce ChAT proteins. Transplantation of the stem cells increased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), enhanced expression of Trk B, and restored host microtubule-associated protein 2 and cholinergic nervous system. The results demonstrate that human NSCs over-expressing ChAT improve cognitive function and physical activity of aging mice, not only by producing ACh directly but also by restoring cholinergic neuronal integrity, which might be mediated by neurotrophins BDNF and NGF.

MeSH Terms

  • Acetylcholine
  • Aging
  • Animals
  • Brain
  • Choline O-Acetyltransferase
  • Cognition Disorders
  • Gene Expression Regulation, Developmental
  • Humans
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred ICR
  • Motor Activity
  • Neural Stem Cells
  • Neurofilament Proteins
  • Receptors, Cholinergic
  • Time Factors
  • Transfection

Keywords

  • Acetylcholine
  • Aging
  • Brain-derived neurotrophic factor
  • Choline acetyltransferase
  • Cognitive function
  • Human neural stem cell
  • Nerve growth factor
  • Physical activity


Probing the early development of visual working memory capacity with functional near-infrared spectroscopy.

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


Quantification of in vivo oxidative damage in Caenorhabditis elegans during aging by endogenous F3-isoprostane measurement.

Oxidative damage is thought to be a major cause in development of pathologies and aging. However, quantification of oxidative damage is methodologically difficult. Here, we present a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach for accurate, sensitive, and linear in vivo quantification of endogenous oxidative damage in the nematode Caenorhabditis elegans, based on F3-isoprostanes. F3-isoprostanes are prostaglandin-like markers of oxidative damage derived from lipid peroxidation by Reactive Oxygen Species (ROS). Oxidative damage was quantified in whole animals and in multiple cellular compartments, including mitochondria and peroxisomes. Mutants of the mitochondrial electron transport proteins mev-1 and clk-1 showed increased oxidative damage levels. Furthermore, analysis of Superoxide Dismutase (sod) and Catalase (ctl) mutants uncovered that oxidative damage levels cannot be inferred from the phenotype of resistance to pro-oxidants alone and revealed high oxidative damage in a small group of chemosensory neurons. Longitudinal analysis of aging nematodes revealed that oxidative damage increased specifically with postreproductive age. Remarkably, aging of the stress-resistant and long-lived daf-2 insulin/IGF-1 receptor mutant involved distinct daf-16-dependent phases of oxidative damage including a temporal increase at young adulthood. These observations are consistent with a hormetic response to ROS.

MeSH Terms

  • Aging
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Catalase
  • Cytochromes b
  • Forkhead Transcription Factors
  • Gene Expression
  • Insulin
  • Isoprostanes
  • Mitochondria
  • Mutation
  • Oxidation-Reduction
  • Peroxisomes
  • Reactive Oxygen Species
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • Sensory Receptor Cells
  • Succinate Dehydrogenase
  • Superoxide Dismutase
  • Transcription Factors


Gene promoter methylation is associated with lung function in the elderly: the Normative Aging Study.

Lung function is a strong predictor of mortality. While inflammatory markers have been associated with lung function decrease, pathways are still poorly understood and epigenetic changes may participate in lung function decline mechanisms. We studied the cross-sectional association between DNA methylation in nine inflammatory genes and lung function in a cohort of 756 elderly men living in the metropolitan area of Boston. Participants donated a blood sample for DNA methylation analysis and underwent spirometry at each visit every 3 to 5 y from 1999-2006. We used separate multivariate mixed effects regression models to study the association between each lung function measurement and DNA methylation within each gene. Decreased CRAT, F3 and TLR2 methylation was significantly associated with lower lung function. One interquartile range (IQR) decrease in DNA methylation was associated with lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1), respectively by 2.94% (p < 10 (-4)) and 2.47% (p < 10 (-3)) for F3, and by 2.10% (p < 10 (-2)) and 2.42% (p < 10 (-3)) for TLR2. Decreased IFNγ and IL6 methylation was significantly associated with better lung function. One IQR decrease in DNA methylation was associated with higher FEV 1 by 1.75% (p = 0.02) and 1.67% (p = 0.05) for IFNγ and IL6, respectively. These data demonstrate that DNA methylation may be part of the biological processes underlying the lung function decline and that IFNγ and IL6 may have ambivalent roles through activation of negative feedback.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Cross-Sectional Studies
  • DNA Methylation
  • Epigenesis, Genetic
  • Humans
  • Inflammation
  • Lung
  • Male
  • Oxidative Stress
  • Promoter Regions, Genetic
  • Regression Analysis
  • Spirometry


Aging and epigenetics: longitudinal changes in gene-specific DNA methylation.

DNA methylation has been associated with age-related disease. Intra-individual changes in gene-specific DNA methylation over time in a community-based cohort has not been well described. We estimated the change in DNA methylation due to aging for nine genes in an elderly, community-dwelling cohort of men. Seven hundred and eighty four men from the Veterans Administration Normative Aging Study who were living in metropolitan Boston from 1999-2009 donated a blood sample for DNA methylation analysis at clinical examinations repeated at approximately 3-5 year intervals. We used mixed effects regression models. Aging was significantly associated with decreased methylation of GCR, iNOS and TLR2 and with increased methylation of IFNγ, F3, CRAT and OGG. Obstructive pulmonary disease at baseline modified the effect of aging on methylation of IFNγ (interaction p = 0.04). For participants who had obstructive pulmonary disease at their baseline visit, the rate of change of methylation of IFNγ was -0.05% 5-methyl-cytosine (5-mC) per year (95% CI: -0.22, 0.13), but was 0.14% 5-mC per year (95% CI: 0.05, 0.24) for those without this condition. Models with random slopes indicated significant heterogeneity in the effect of aging on methylation of GCR, iNOS and OGG. These findings suggest that DNA methylation may reflect differential biological aging.

MeSH Terms

  • Aged
  • Aging
  • Boston
  • Cohort Studies
  • DNA Methylation
  • Epigenesis, Genetic
  • Humans
  • Longitudinal Studies
  • Male
  • United States
  • United States Department of Veterans Affairs


Prevalence of insomnia and its relationship to the health habits or status of women living along a city road part 1. epidemiologie study.

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


Influences of brain development and ageing on cortical interactive networks.

To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Brain
  • Brain Mapping
  • Cerebral Cortex
  • Child
  • Child, Preschool
  • Electroencephalography
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Nerve Net
  • Pilot Projects


Cella media distance in human brain in relation to age and gender.

To determine whether simple linear measurements can be used as an accurate and reproducible replacement of the volumetric ones. We measured the cella media distance (CM1) and the distance between the right and left human brain surfaces (CM2)--measured along the CM1 line--in the groups of women (F) and men (M) who were divided according to diagnoses into three subgroups (F1-3 and M1-3). Examinations were carried out under standardized conditions: axial serial CT (Computed Tomography) images, in 4 mm layers (333 patients). Measured values were detected by Osiris Software. Recorded values were statistically analysed. We found very highly significant (subgroups M1, M3), and significant (subgroups F1, F2, F3, M2) associations between the cella media distance and the decade of age. There were only non-significant differences in CM1 distances between men and women and between the diagnoses groups as well. Correlation between cella media distance and volume of lateral ventricles was greater in men in both, subgroup M1 (r = 0.659, P < 0.0001) and in a mixed group where all the three male subgroups M1-3 were combined into one group (r = 0.675, P < 0.0001). Among women the correlation was lower, however still significant (r = 0.357, P < 0.0001 for F1 and r = 0.465, P < 0.0001 for F1-3). The cella media distance is much better predictor of brain lateral ventricular volume in men than in women.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Brain
  • Cerebral Ventricles
  • Female
  • Humans
  • Male
  • Middle Aged
  • Organ Size
  • Sex Characteristics
  • Tomography, X-Ray Computed
  • Young Adult


Age-dependent role of steroids in the regulation of growth of the hen follicular wall.

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


Pre-movement gating of somatosensory-evoked potentials by self-initiated movements: the effects of ageing and its implication.

To study whether the gating effect of the self-initiated movements on the cortical somatosensory-evoked potentials (SEPs) is affected by ageing. The SEPs elicited by stimulating the right median nerve were recorded in 14 young and 16 older healthy subjects, while self-initiated movements of the right fingers were performed at 5-10 s intervals. The amplitudes of the major components of the SEPs at F3 and C3' (2 cm posterior to C3) during the pre-movement period were analysed as the resting condition subserving the baseline. The amplitudes at rest were significantly greater in the elderly than in the younger subjects. The amplitudes of P27, N35 and P45 at C3' as well as N30 at F3 decreased significantly during the pre-movement period. However, the ratio of amplitudes in the pre-movement period to the resting period in the elderly was not significantly different from that in the younger subjects, except for the interaction of N30. The effect of age on the gating of N30 at F3 may indicate an altered preparatory processing of self-initiated movement in the elderly. The gating effect of older subjects at C3' is almost comparable to that of young ones, which appears to be a compensatory mechanism to maintain the precise movements. Ageing affects the SEPs differently at rest and pre-movement gating.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Analysis of Variance
  • Electric Stimulation
  • Evoked Potentials, Somatosensory
  • Female
  • Fingers
  • Humans
  • Male
  • Median Nerve
  • Middle Aged
  • Motor Activity
  • Movement
  • Rest
  • Sensory Gating


Distinguishing childhood absence epilepsy patients from controls by the analysis of their background brain electrical activity.

Background electroencephalography (EEG), recorded with scalp electrodes, in children with childhood absence epilepsy (CAE) and control individuals has been analyzed. We considered 5 CAE patients, all right-handed females and aged 6-8 years. The 15 control individuals had the same characteristics of the CAE ones, but presented a normal EEG. The EEG was obtained using bipolar connections from a standard 10-20 electrode placement (Fp1, Fp2, F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4, T6, O1 and O2). Recordings were undertaken in the resting state with eyes closed. EEG hallmarks of absence seizure activity are widely accepted, but there is a recognition that the bulk of interictal EEG in CAE appears normal to visual inspection. The functional activity between electrodes was evaluated using a wavelet decomposition in conjunction with the Wootters distance. Then, pairs of electrodes with differentiated behavior between CAE and controls were identified using a test statistic-based feature selection technique. This approach identified clear differences between CAE and healthy control background EEG in the frontocentral electrodes, as measured by Principal Component Analysis. The findings of this pilot study can have strong implications in future clinical practice.

MeSH Terms

  • Age Factors
  • Aging
  • Brain Mapping
  • Cerebral Cortex
  • Child
  • Diagnosis, Differential
  • Electrodes
  • Electrodiagnosis
  • Electroencephalography
  • Epilepsy, Absence
  • Evoked Potentials
  • Female
  • Humans
  • Predictive Value of Tests
  • Reference Values


Effects of ginsenosides, active ingredients of Panax ginseng, on development, growth, and life span of Caenorhabditis elegans.

The backbone structure of ginsenosides, active ingredients of Panax ginseng, is similar with that of sterol, especially cholesterol. Caenorhabditis elegans (C. elegans) is one of free living nematodes and is well-established animal model for biochemical and genetic studies. C. elegans cannot synthesize de novo cholesterol, although cholesterol is essential requirement for its growth and development. In the present study, we investigated the effects of ginseng total saponins (GTS) on the average brood size, growth, development, worm size, and life span of C. elegans in cholesterol-deprived and -fed medium. Cholesterol deprivation caused damages on normal growth, reproduction, and life span of worms throughout F1 to F3 generations. GTS supplement to cholesterol-deprived medium restored the growth, reproduction, and life span of worms as much as cholesterol alone-fed medium. GTS co-supplement to cholesterol-fed medium not only promoted worm reproduction but also induced bigger worms and faster growth than cholesterol-fed medium. In study to identify which ginsenosides are responsible for life span restoring effects of GTS, we found that ginsenoside Rc supplement not only restored life span of worms grown in cholesterol-deprived medium but also prolonged life span of worms grown in cholesterol-fed medium. Worms grown in medium supplemented with ginsenoside Rb(1) or Rc to cholesterol-deprived medium exhibited strong filipin staining, in which filipin forms tight and specific complexes with 3beta-hydroxy sterols. These results show a possibility that ginsenosides could be utilized by C. elegans as a sterol substitute and further indicate that ginsenoside Rc is the component of Panax ginseng that prolongs the life span of C. elegans.

MeSH Terms

  • Animals
  • Caenorhabditis elegans
  • Ginsenosides
  • Longevity
  • Molecular Structure
  • Panax


Age, sex, and vowel dependencies of acoustic measures related to the voice source.

The effects of age, sex, and vocal tract configuration on the glottal excitation signal in speech are only partially understood, yet understanding these effects is important for both recognition and synthesis of speech as well as for medical purposes. In this paper, three acoustic measures related to the voice source are analyzed for five vowels from 3145 CVC utterances spoken by 335 talkers (8-39 years old) from the CID database [Miller et al., Proceedings of ICASSP, 1996, Vol. 2, pp. 849-852]. The measures are: the fundamental frequency (F0), the difference between the "corrected" (denoted by an asterisk) first two spectral harmonic magnitudes, H1* - H2* (related to the open quotient), and the difference between the "corrected" magnitudes of the first spectral harmonic and that of the third formant peak, H1* - A3* (related to source spectral tilt). The correction refers to compensating for the influence of formant frequencies on spectral magnitude estimation. Experimental results show that the three acoustic measures are dependent to varying degrees on age and vowel. Age dependencies are more prominent for male talkers, while vowel dependencies are more prominent for female talkers suggesting a greater vocal tract-source interaction. All talkers show a dependency of F0 on sex and on F3, and of H1* - A3* on vowel type. For low-pitched talkers (F0 < or = 175 Hz), H1* - H2* is positively correlated with F0 while for high-pitched talkers, H1* - H2* is dependent on F1 or vowel height. For high-pitched talkers there were no significant sex dependencies of H1* - H2* and H1* - A3*. The statistical significance of these results is shown.

MeSH Terms

  • Adolescent
  • Adult
  • Age Factors
  • Aging
  • Child
  • Female
  • Humans
  • Larynx
  • Male
  • Models, Biological
  • Phonation
  • Phonetics
  • Speech Acoustics
  • Voice
  • Voice Quality


Electroencephalographic approximate entropy changes in healthy volunteers during remifentanil infusion.

The aim of this study was to investigate the independent effect of remifentanil on the approximate entropy (ApEn) in frontoparietal montages. The authors investigated which montages were relevant to assess the remifentanil effect on the electroencephalogram. Spectral edge frequency and the canonical univariate parameter were used as comparators. Twenty-eight healthy volunteers were enrolled. With recording of the electroencephalogram at the F3, F4, Cz, P3, and P4 montages, remifentanil was infused at the rate of 1-8 mug . kg . min for 15-20 min. The relation between remifentanil concentration and the electroencephalographic parameters were tested by Spearman correlation. Signal-to-noise ratio, artifact robustness, coefficient of variation of the median baseline and maximal electroencephalographic effects, and ratio of average maximal electroencephalographic effect to interindividual baseline variability were measured. The performance of ApEn as an index of remifentanil effect site concentrations was tested by prediction probability. Approximate entropy showed significant correlation (R = -0.6465, P < 0.0001) with remifentanil concentration. It provided comparable signal-to-noise ratio, artifact robustness, and ratio of average maximal electroencephalographic effect to interindividual baseline variability to 95% spectral edge frequency. The coefficients of variation of the median baseline and maximal electroencephalo graphic effects were smallest in ApEn. Parietal montages showed higher ratios of average maximal electroencephalographic effect to interindividual baseline variability for all electroencephalographic parameters and lower coefficients of variation of the baseline values for ApEn and 95% spectral edge frequency than frontal montages. The prediction probability of ApEn was 0.7730. Approximate entropy derived from a parietal montage is appropriate for the assessment of the remifentanil effect on the electroencephalogram.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Algorithms
  • Analgesics, Opioid
  • Artifacts
  • Bayes Theorem
  • Data Interpretation, Statistical
  • Electroencephalography
  • Entropy
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Infusions, Intra-Arterial
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Models, Statistical
  • Piperidines
  • Remifentanil


Application of Cutometer area parameters for the study of human skin fatigue.

The age-related decrease of skin elasticity results in larger fatigue of adult skin than young skin after applying multiple stress at one and the same anatomic region. The aim of this study was to compare the informativeness of Cutometer standard R-parameters with new area parameters regarding the age-related changes in human skin fatigue. A total of 40 healthy volunteers aged 12-82 years were studied. Mechanical parameters of the skin were determined using a non-invasive suction skin elasticity meter (Cutometer). Measurements were made on the temporal region and volar forearm. Skin mechanical parameters analyzed by Win-Cutometer MPA software were R3, R4 and R9 (R-parameters), and F2 and F3 (area parameters). The adult skin was characterized by significantly higher values of R4, R9 and F2, and lower F3 compared with young skin. R3 was not significantly altered. There were not any sex-related differences. F2 correlated positively with parameters R3, R4 and R9, while F3 correlated negatively with R4. A positive correlation within the parameters R3, R4 and R9 was established at both anatomic regions. The non-invasive method applied can be useful for objective and quantitative investigation of age-related changes in skin fatigue and evaluation of the effects of cosmetic and anti-aging topical products. The mechanical parameters R4 and F3 are most indicative of human skin fatigue.

MeSH Terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Algorithms
  • Child
  • Diagnosis, Computer-Assisted
  • Elasticity
  • Female
  • Hardness
  • Hardness Tests
  • Humans
  • Male
  • Middle Aged
  • Physical Examination
  • Physical Stimulation
  • Sex Factors
  • Skin Physiological Phenomena


Delayed motherhood decreases life expectancy of mouse offspring.

This study analyzes the long-term effects of delayed motherhood on reproductive fitness and life expectancy of offspring in the mouse. Hybrid (C57BL/6JIco x CBA/JIco) first-generation (F1) females, either at the age of 10 or 51 wk, were individually housed with a randomly selected 12- to 14-wk-old hybrid male following a breeding pen system until females reached the end of their reproductive life. Reproductive fitness of second-generation (F2) females was tested from the age of 25 wk until the end of their reproductive life. In F2 males, the testing period ranged from the age of 52 wk until their natural death. Delayed motherhood of hybrid F1 female mice was associated with a decreased percentage of male F3 offspring at birth and lower life expectancy and body weight during adulthood of F2 offspring. There was, however, no evident negative effect of delayed motherhood on several reproductive fitness variables in either male or female F2 offspring. This included between-parturition interval, litter size at birth and at weaning, body weight at weaning and preweaning mortality of F3 pups, percentage of F3 litters with at least one pup cannibalized, and time at which female and male F2 offspring ceased their reproductive life. These data clearly show that delayed motherhood in the mouse is associated with negative long-term effects on offspring survival.

MeSH Terms

  • Animals
  • Body Weight
  • Female
  • Life Expectancy
  • Litter Size
  • Longevity
  • Male
  • Mice
  • Mice, Inbred Strains
  • Pregnancy
  • Reproduction
  • Sex Ratio


Fitness cost of resistance to cadmium in the least killifish (Heterandria formosa).

Fitness costs constrain the evolution of resistance to environmental stress in populations. We earlier reported on a rapid response to laboratory selection for cadmium resistance in the least killifish (Heterandria formosa). By the sixth generation, the three selection populations were threefold more resistant to cadmium than the control populations. Here, we report the fitness costs and trade-offs associated with this evolution of resistance. In the F3 and F4 generations, the selection populations produced smaller-sized offspring than the control populations. A comprehensive life-history traits study in the F7 generation showed that the selection populations had, on average, an 18% decrease in fecundity. The selection populations also had a smaller brood size, longer time to first reproduction, and shorter female life expectancy than the control populations. Our results strongly suggest that fitness costs and trade-offs were associated with the evolution of resistance to cadmium in the least killifish. The fitness costs and trade-offs may result from maintenance of the underlying resistance mechanisms, leading to changes in resource allocation in the cadmium-adapted fish.

MeSH Terms

  • Adaptation, Physiological
  • Animals
  • Biological Evolution
  • Cadmium
  • Drug Resistance
  • Female
  • Fertility
  • Fundulidae
  • Longevity
  • Male


Age effects on visual EEG responses reveal distinct frontal alpha networks.

The present study aimed to describe the effect of aging on single-trial visual alpha responses. Visual evoked potentials were recorded at F3, Cz, P3, and O1 in 12 young (20-30-year-olds) and in 10 middle-aged adults (50-55-year-olds). Slow (7-10 Hz) and fast (10-15 Hz) alpha frequency bands were analyzed. Three parameters of single alpha responses were assessed for the 0-300 ms period after stimulus: (i) maximal single-sweep amplitude; (ii) phase-locking with stimulus, and (iii) enhancement of post-stimulus relative to pre-stimulus alpha activity. Ongoing alpha activity at anterior sites was larger in middle-aged subjects. Age differences in response amplitude depended on the anterior shift of ongoing alpha activity. Over fronto-central areas, the phase-locking of fast alpha responses was significantly increased, whereas the phase-locking of slow alpha responses was decreased in middle-aged compared to young adults, independently of amplitude. In contrast to slow alpha responses, frontal and occipital fast alpha responses were interrelated. These observations are in accordance with previous findings from the auditory modality implying that the age-related changes in frontal alpha oscillations are modality-independent. Slow and fast frontal alpha responses were affected differentially by the age, which might reflect the activations of functionally distinct alpha networks.

MeSH Terms

  • Adolescent
  • Adult
  • Aging
  • Alpha Rhythm
  • Evoked Potentials, Visual
  • Frontal Lobe
  • Humans
  • Middle Aged
  • Occipital Lobe
  • Photic Stimulation
  • Regression Analysis


Effect of nonylphenol on serum testosterone levels and testicular steroidogenic enzyme activity in neonatal, pubertal, and adult rats.

Previous dose range-finding studies with nonylphenol (NP) administered to rats in a soy- and alfalfa-free diet showed apparent feminization of several endpoints in male rats at doses of 25 ppm and above. One possible mechanism contributing to these effects is a reduction of testosterone at critical developmental periods. The present study was conducted as an adjunct to a multigeneration study and was designed to examine the effect of NP on testosterone production. Male rats in the F1 and F2 generations were exposed through their dams or directly to various dietary doses of NP (0, 25, 200 and 750 ppm) throughout gestation and until sacrifice at either postnatal day 2 (PND2), PND50, or PND140. Male pups in the F3 generation were examined only on PND2. At PND2, serum testosterone levels were significantly decreased in all groups exposed to NP in the F1 generation, but not in the F2 or F3 generations. The activity of 17alpha-hydroxylase/C17, 20 lyase (P450c17) in PND2 testicular homogenates was not affected by NP treatment. In F1 and F2 PND50 and PND140 rats, NP treatment did not affect serum testosterone levels. The absolute dorsolateral prostate weight was increased in the 200 and 750 ppm dose groups only in the F1 PND50 rats, however, no significant effects were observed in other male reproductive organs. NP treatment did not affect P450c17 activity in microsomes prepared from testes of F1 PND50 or PND140 rats. However, P450c17 activity was significantly decreased in testicular microsomes of F(2) PND50 (200 and 750 ppm dose groups) and PND140 (25, 200, and 750 ppm dose groups) rats. A decrease in testicular beta-nicotinamide adenine dinucleotide phosphate (NADPH) P450 reductase was also observed in all PND50 and PND140 NP-exposed rats of the F1 and F2 generations. The ability of NP to directly inhibit P450c17 activity in vitro at concentrations of 1-100 microM was also demonstrated. These results indicate that NP can inhibit the activity of enzymes involved in testosterone synthesis, but suggest minimal effects on testosterone or testosterone-dependent endpoints via this mechanism.

MeSH Terms

  • Aging
  • Animals
  • Blotting, Western
  • Body Weight
  • Chromatography, High Pressure Liquid
  • Diet
  • Male
  • NADPH-Ferrihemoprotein Reductase
  • Organ Size
  • Phenols
  • Rats
  • Sex Characteristics
  • Steroid 17-alpha-Hydroxylase
  • Testis
  • Testosterone


Chronic nutritional deprivation of n-3 alpha-linolenic acid does not affect n-6 arachidonic acid recycling within brain phospholipids of awake rats.

Using an in vivo fatty acid model and operational equations, we reported that esterified and unesterified concentrations of docosahexaenoic acid (DHA, 22 : 6 n-3) were markedly reduced in brains of third-generation (F3) rats nutritionally deprived of alpha-linolenic acid (18 : 3 n-3), and that DHA turnover within phospholipids was reduced as well. The concentration of docosapentaenoic acid (DPA, 22 : 5 n-6), an arachidonic acid (AA, 20 : 4 n-6) elongation/desaturation product, was barely detectable in control rats but was elevated in the deprived rats. In the present study, we used the same in vivo model, involving the intravenous infusion of radiolabeled AA to demonstrate that concentrations of unesterified and esterified AA, and turnover of AA within phospholipids, were not altered in brains of awake F3-generation n-3-deficient rats, compared with control concentrations. Brain DPA-CoA could be measured in the deprived but not control rats, and AA-CoA was elevated in the deprived animals. These results indicated that AA and DHA are recycled within brain phospholipids independently of each other, suggesting that recycling is regulated independently by AA- and DHA-selective enzymes, respectively. Competition among n-3 and n-6 fatty acids within brain probably does not occur at the level of recycling, but at levels of elongation and desaturation (hence greater production of DPA during n-3 deprivation), or conversion to bioactive eicosanoids and other metabolites.

MeSH Terms

  • Acyl Coenzyme A
  • Aging
  • Animals
  • Arachidonic Acid
  • Body Weight
  • Brain Chemistry
  • Chromatography, High Pressure Liquid
  • Diet
  • Docosahexaenoic Acids
  • Fatty Acids, Nonesterified
  • Female
  • Male
  • Phospholipids
  • Rats
  • Rats, Long-Evans
  • alpha-Linolenic Acid


Generation dependent reduction of tTA expression in double transgenic NZL-2/tTA(CMV) mice.

Despite the overall successful application of the tet-system to regulate gene expression in vitro and in vivo, nothing is known so far about the long-term stability of this system in transgenic mice. In this study, mice of generation F2, F3, F4, or F10 of two independent tTA(CMV) transgenic lines were bred with NZL-2 mice containing a tTA-responsive bidirectional promoter that allows the simultaneous expression of two reporter genes encoding luciferase and beta-galactosidase. Analysis of the expression of transgenes in double transgenic mice revealed a dramatic reduction of tTA transactivator mRNA over time. As a consequence, the expression of both reporter genes was gradually reduced from generation to generation in tissues of embryonic and adult NZL-2/tTA(CMV) mice. Luciferase activity in NZL-2/tTA(CMV)(F10) mice was reduced 8-10-fold compared to NZL-2/ tTA(CMV)(F2) mice, and beta-galactosidase expression was no longer detectable. In summary, we describe the long-term instability of the tet-system in our NZL-2/tTA(CMV) double transgenic mice. The molecular basis of this observation and experimental tools to overcome this limitation need to be addressed in future.

MeSH Terms

  • Aging
  • Animals
  • Blotting, Southern
  • Crosses, Genetic
  • Embryo, Mammalian
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genes, Reporter
  • Luciferases
  • Male
  • Mice
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Tetracycline
  • Time Factors
  • Transgenes
  • beta-Galactosidase


The Hebrew vowel system: raw and normalized acoustic data.

It is well known that different languages use different vowel systems in terms of variety and number. The Hebrew vowel system consists of five vowels /i, e, a, o, u/. The present research identified the acoustic features of the vowels produced by Hebrew speakers differing in age and sex. Ninety speakers (men, women, boys, and girls) were recorded. The vowels were presented in a nonword context that was placed in a meaningful Hebrew sentence. The data included measurements of F0, F1, F2, F3, F4, and vowel duration for the five different vowels produced by the four groups of participants. Conversion of the physical frequency measures of formants into a critical band (bark) scale was performed as well. The results indicated that the F2/F1 ratio is a distinctive feature of all five vowels, keeping with the findings of previous research in other languages. Nevertheless, the values of the F2/F1 ratios led to an overlap between different vowels produced by different groups of speakers. Applying the bark transformation as speaker normalization procedure succeeded in reducing speaker differences while increasing vowel differences.

MeSH Terms

  • Adult
  • Aging
  • Child
  • Female
  • Humans
  • Male
  • Phonetics
  • Speech
  • Speech Acoustics


Reduced activation of midline frontal areas in human elderly subjects: a contingent negative variation study.

Contingent negative variation (CNV) was recorded from electrodes F7, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4 and P8 in 19 young (mean age: 23 years) and 15 elderly (mean age: 66 years) healthy right-handed subjects, using a S2-choice paradigm. Young subjects showed early peak negativity shortly after the warning stimulus over mid-frontal areas, whereas for the remaining electrodes the negativity increased continuously. The amplitude of the early CNV was selectively reduced in elderly subjects over midline but not lateral frontal areas. We conclude that the activation of frontal midline areas as pre-supplementary motor area or anterior cingulate might be impaired in higher age.

MeSH Terms

  • Acoustic Stimulation
  • Adult
  • Aged
  • Aging
  • Analysis of Variance
  • Electroencephalography
  • Female
  • Frontal Lobe
  • Humans
  • Male
  • Middle Aged
  • Parietal Lobe
  • Reaction Time


Influence of aging and cell senescence on telomerase activity in keratinocytes.

Telomeres, which exist in eukaryotic chromosome ends in specialized G-rich TTAGGG structure, protect the ends from degradation or fusion. On the other hand, telomerase is a ribonucleoprotein complex enzyme that synthesizes TTAGGG repeat sequences at the ends of eukaryotic chromosomes. Previous studies suggested that telomere length and telomerase activity cooperate in aging and immortalization of cells. Here, we examined telomere length and telomerase activity in keratinocytes from seven human subjects, including a patient with Werner's syndrome. Telomere length in keratinocytes from healthy individuals was shortened with aging. However, telomerase activity from an individual aged 42 years was reduced, compared with that from a 0 year old individual. Passages of keratinocytes reduced telomerase activity significantly in F2 and F3 keratinocytes from 0 and 42 year old individuals. Withdrawal of either EGF or amphiregulin from medium resulted in down-regulation of telomerase activity. These results suggest that telomere length and telomerase activity in primary cultured keratinocytes may be one of the parameters for cell senescence. However, there remain obscure factors such as ultraviolet-B radiation and growth factors.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Cells, Cultured
  • Cellular Senescence
  • Child
  • Female
  • Humans
  • Infant
  • Keratinocytes
  • Male
  • Middle Aged
  • Telomerase


Regional distribution and cell type-specific expression of the mouse F3 axonal glycoprotein: a developmental study.

The expression of the mouse axonal adhesive glycoprotein F3 and of its mRNA was studied on sections of mouse cerebellar cortex, cerebral cortex, hippocampus, and olfactory bulb from postnatal days 0 (P0) to 30 (P30). In cerebellar cortex, a differential expression of F3 in granule versus Purkinje neurons was observed. F3 was highly expressed during migration of and initial axonal growth from cerebellar granule cells. The molecule was then downregulated on cell bodies and remained expressed, although at low levels, on their axonal extensions. On Purkinje cells, F3 was strongly expressed on cell bodies and processes at the beginning of the second postnatal week; by P16 it was restricted to neurites of Purkinje cells subpopulations. In the cerebral cortex, the molecule was highly expressed on migrating neurons at P0; by P16, it was found essentially within the neuropil with a diffuse pattern. In the hippocampal formation, where F3 was expressed on both pyramidal and granule neurons, a clear shift from the cell bodies to neurite extensions was observed on P3. In the olfactory pathway, F3 was expressed mainly on olfactory nerve fibers, mitral cells, and the synaptic glomeruli from P0 to P3, with a sharp decline from P11 to P16. As a whole, the data show that F3 protein expression is regulated at the regional, cellular, and subcellular levels and suggest that, in different regions, it can be proposed as a reliable neuronal differentiation marker.

MeSH Terms

  • Aging
  • Animals
  • Animals, Newborn
  • Axons
  • Brain
  • Cell Adhesion Molecules, Neuronal
  • Cerebellar Cortex
  • Cerebral Cortex
  • Contactins
  • Gene Expression Regulation, Developmental
  • Hippocampus
  • Mice
  • Neurons
  • Olfactory Bulb
  • Purkinje Cells
  • RNA, Messenger
  • Transcription, Genetic


The epithelial cell response to rotavirus infection.

Rotavirus is the most important worldwide cause of severe gastroenteritis in infants and young children. Intestinal epithelial cells are the principal targets of rotavirus infection, but the response of enterocytes to rotavirus infection is largely unknown. We determined that rotavirus infection of HT-29 intestinal epithelial cells results in prompt activation of NF-kappaB (<2 h), STAT1, and ISG F3 (3 h). Genetically inactivated rotavirus and virus-like particles assembled from baculovirus-expressed viral proteins also activated NF-kappaB. Rotavirus infection of HT-29 cells induced mRNA for several C-C and C-X-C chemokines as well as IFNs and GM-CSF. Mice infected with simian rotavirus or murine rotavirus responded similarly with the enhanced expression of a profile of C-C and C-X-C chemokines. The rotavirus-stimulated increase in chemokine mRNA was undiminished in mice lacking mast cells or lymphocytes. Rotavirus induced chemokines only in mice <15 days of age despite documented infection in older mice. Macrophage inflammatory protein-1beta and IFN-stimulated protein 10 mRNA responses occurred, but were reduced in p50-/- mice. Macrophage inflammatory protein-1beta expression during rotavirus infection localized to the intestinal epithelial cell in murine intestine. These results show that the intestinal epithelial cell is an active component of the host response to rotavirus infection.

MeSH Terms

  • Aging
  • Animals
  • Chemokines
  • Cytokines
  • DNA-Binding Proteins
  • Diarrhea
  • Enzyme Inhibitors
  • Epithelial Cells
  • Gene Expression Regulation
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nuclear Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-kit
  • RNA, Viral
  • Rotavirus
  • Rotavirus Infections
  • Transcription Factors
  • Transcriptional Activation
  • Transposases


Abnormally high nourishment during sensitive periods results in body weight changes across generations.

This study asked whether a brief period of overnutrition during a developmentally sensitive time could impact the individual's adult weight and that of succeeding generations. Female rat pups (F1 generation) were randomly assigned to 1 of 3 groups: (1) a control group that was naturally reared by mothers; (2) another control group implanted with chronic gastric fistulas on postnatal day 4 and fed enough formula to match the growth of the mother-reared group; and (3) an experimental group gastrostomized and infused from day 8 through day 16 with a greater quantity of food than gastrostomy-reared controls (OF). On postnatal day 16, both gastrostomy-reared groups were returned to normal litters. Adult F1 females from overfed and mother-reared groups were bred with normal males to yield an F2 generation. F2 adult females were bred to normal males to produce an F3 generation. When adult, the F1 experimental group was heavier than control groups. F2 adults from OF mothers were smaller than those from the control group. F3 animals from OF grandmothers were heavier at weaning than F3 descendants from mother-reared animals. Excess nourishment during a developmentally sensitive period changed the metabolic phenotype of one generation so dramatically that the gestational development and subsequent phenotype of two succeeding generations were also changed. The experiment models fetal effects of gestational diabetes in humans and may help to elucidate how, independent of genetic anomalies, secular changes can be detected across generations.

MeSH Terms

  • Aging
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Animals, Newborn
  • Body Weight
  • Enteral Nutrition
  • Female
  • Food, Formulated
  • Gastric Fistula
  • Gastrostomy
  • Male
  • Milk
  • Rats
  • Rats, Long-Evans


Age-related decline of F3/contactin in rat hippocampus.

F3/Contactin (F3), a neural adhesion molecule, is known to be involved in developmental and regenerative processes in the brain. We have investigated age-related change in the expression of F3 mRNA and protein in the Wistar rat brain using immunohistochemistry and in situ hybridization. From 3 months to 24 months, no obvious change in the amount of F3 protein was observed in cerebral cortex, hippocampus and cerebellum. However, in 30-month-old rats a significant decrease in F3 protein was found in the hippocampus. A specific decrease of density of F3 immunostaining and F3 mRNA expression was observed in the pyramidal neurons of CA1 and the granule cells in dentate gyrus. The specific decrease of F3 in the hippocampus at late stage of aging may be related to memory deficient in old age.

MeSH Terms

  • Aging
  • Animals
  • Cell Adhesion Molecules, Neuronal
  • Contactins
  • Hippocampus
  • Immunohistochemistry
  • Rats
  • Rats, Wistar


Body weight and egg weight dynamics in layers.

The association between body weight-age and egg weight-age patterns was studied in a segregating population of laying hens belonging to the F3 generation of a Rhode Island Red x White Leghorn reciprocal cross. Body weight and egg weight were expressed as a function of time using the model developed by Weatherup and Foster. Each hen was characterized in terms of its asymptotic body weight (ABW), maturing rate for body weight (MBW), asymptotic egg weight (AEW), and maturing rate for egg weight (MEW) values. Four groups of hens were distinguished by means of a principal component analysis. Birds belonging to Groups 1 and 3 were discriminated for their egg weight-age pattern. Group 1 included hens laying the heaviest eggs (AEW = 66.1 g) at the lowest maturing rate (MEW = 0.922), the inverse being true for birds in Group 3 (AEW = 55.7 g and MEW = 0.737). Birds belonging to Groups 2 and 4 were distinguished for their body weight-age pattern. Hens in Group 2 showed the lowest ABW (1,893 g) and MBW (0.764) whereas the heaviest (ABW = 2,802 g) and less mature (MBW = 0.929) birds were found in Group 4. The results confirm the partial pleiotropic basis of the body weight-egg weight correlation, evincing the feasibility of applying selective pressure not only on each character separately but also on maturing rate independently of asymptotic weight within each trait. This strategy could be implemented using a biological selection index based on principal component analysis equations.

MeSH Terms

  • Aging
  • Animals
  • Body Weight
  • Chickens
  • Crosses, Genetic
  • Eggs
  • Female
  • Least-Squares Analysis
  • Oviposition


Age-related changes in structure and relative collagen content of the human and feline sinoatrial node. A comparative study.

Age-related changes in the structure and size of the human and cat sinoatrial nodes were studied by light microscopy, with emphasis on changes in relative collagen volume. Sinoatrial nodes from 41 humans (aged 0-94 years) and 21 cats (aged 6 weeks-18 years) were used. It was found that there were no changes in the dimensions of the sinoatrial node during adult life in either species. In Sirius Red F3 Ba stained sections, the relative volume of collagen was measured using an interactive image analysis system. The relative volume of collagen in the human sinoatrial node increases from 38% during childhood to 70% during adulthood. Once adulthood is reached, there are no further changes in the relative volume of collagen. In the cat sinoatrial node the relative volume of collagen is only 27% and does not change with age. The organisation of collagen in the sinoatrial node, however, demonstrates an age-dependent change in both humans and cats. From coarse strands between clusters of nodal cells it gradually changes into a fine network of isolated collagen fibres which surround individual nodal cells. This process is more pronounced in humans. It is concluded that age-related changes in sinoatrial node function are not related to an increase in collagen content in the sinoatrial node.

MeSH Terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Animals
  • Cats
  • Child
  • Child, Preschool
  • Collagen
  • Humans
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Sinoatrial Node


Nonsteroidal antiinflammatory drugs and cognitive decline in the elderly.

To better define the role of nonsteroidal antiinflammatory drugs (NSAID) in cognitive decline of the elderly. Population based inception cohort of the rural elderly. NSAID user status was characterized as high dose, low/medium dose, or nonuser at 2 successive in-person interviews 3 years apart (F3 and F6). Respondents were from the Iowa 65 Rural Health Study, one of the 4 cohorts of the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly. Memory decline was assessed by a change in immediate word recall between F3 and F6. Multivariable logistic regression models were created to determine important predictors of the F3 to F6 recall memory decline in groups with poor, average, and good word recall at the F3 interview. Specific NSAID were compared to assess which drugs, if any, were associated with memory decline. The 2 factors most strongly associated with a significant immediate word recall decline between F3 and F6 among individuals in the average F3 word recall group were limitation in functional status [odds ratio (OR) = 2.31, 95% Confidence Interval (CI) (1.51, 3.52)] and high dose NSAID use [OR = 2.04, 95% CI (1.07, 3.89)]. No single NSAID agent was significantly more strongly associated with word recall decline than the others. However, in exploratory analyses use of high dose NSAID of the proprionic acid family neared significance for recall decline [OR = 3.17, 95% CI (0.92, 10.9). In elderly respondents with average baseline recall memory, high dose NSAID were a significant risk factor for longitudinal memory decline in this community based cohort. Although a large scale clinical trial is needed to definitely address this issue, we provide further evidence that NSAID play a role in cognitive dysfunction in the elderly.

MeSH Terms

  • Aged
  • Aging
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cognition Disorders
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Forecasting
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Recall
  • Rural Health


Genetic and phenotypic (co)variances for production traits of intact male populations of purebred and composite beef cattle.

Least squares means, genetic (sigma g) and phenotypic (sigma p) standard deviations, and phenotypic coefficients of variation (CV) were estimated for growth traits of intact males from 12 breed groups combined, for nine purebreds combined, and for the F1, F2, F3, and F4 generations of three composite populations to which the nine purebreds contributed. Heritabilities (h2) and genetic (rg) and phenotypic (rp) correlations were estimated for growth traits, calving difficulty of calves with dams of different ages, and gestation length. Coefficients of variation and sigma g generally were similar for composites and contributing purebreds. Generally, estimates of h2 were similar for all breed groups combined, contributing purebreds combined, and composites combined. Estimates of h2 for calving difficulty were higher for calves with 2-yr-old dams than for calves with dams > or = 3 yr old and were sufficiently high (.27 and .31) to be a useful selection criterion for reducing calving difficulty. Mean h2 pooled within all breed groups ranged from .35 for 200-d weight and 368-d weight to .48 for 368-d height. Estimates of h2 for subjective scores of anatomical traits were only slightly lower than those for growth and size traits. The h2 of scrotal circumference (.43) was similar to those for growth and size traits. Genetic correlations between birth weight and calving difficulty were similar for 1) calves with dams of all ages, 2) calves with 2-yr-old dams, and 3) calves with dams > or = 3 yr old.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms

  • Aging
  • Animals
  • Birth Weight
  • Body Constitution
  • Body Weight
  • Cattle
  • Female
  • Genetic Variation
  • Genotype
  • Growth
  • Labor, Obstetric
  • Male
  • Models, Genetic
  • Organ Size
  • Phenotype
  • Pregnancy
  • Reproduction
  • Selection, Genetic
  • Sex Characteristics
  • Statistics as Topic


Genetic and phenotypic (co)variances for production traits of female populations of purebred and composite beef cattle.

Least squares means, genetic and phenotypic standard deviations, and phenotypic coefficients of variation were estimated for growth, size, condition score, age at puberty, gestation length, and calving difficulty as traits of individual females from 12 breed groups combined, for nine purebreds combined, and for the F1, F2, and F3 generations of three composite populations to which the nine purebreds contributed. Heritabilities and genetic and phenotypic correlations were estimated for growth and size traits, age at puberty, gestation length, and calving difficulty of calves with dams of different ages. Coefficients of variation and genetic standard deviations were similar for composites and contributing purebreds for the traits evaluated. Generally, estimates of heritability were similar for all breed groups combined, contributing purebreds combined, and composites combined. Estimates of heritability for calving difficulty were higher for calves with 2-yr-old dams than for calves with dams > or = 3 yr old and were sufficiently high (.33 and .26) to be a useful selection criterion for reducing calving difficulty. Estimate of heritability for age at puberty was .31 and for gestation length was .45. The rg between birth weight and calving difficulty score was higher for calves with 2-yr-old dams (.59) than for calves with dams > or = 3 yr old (.44). The higher genetic correlation between birth weight and calving difficulty score (.59) in calves with 2-yr-old dams than between birth weight and 368-d weight (.33) suggests opportunity to reduce calving difficulty by reducing birth weight while maintaining 368-d weight.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH Terms

  • Aging
  • Animals
  • Birth Weight
  • Body Constitution
  • Body Weight
  • Breeding
  • Cattle
  • Female
  • Genetic Variation
  • Genotype
  • Growth
  • Labor, Obstetric
  • Male
  • Phenotype
  • Pregnancy
  • Reproduction
  • Selection, Genetic
  • Sex Characteristics
  • Sexual Maturation


[The age-dependent dynamics of brain potentials related to movement in 9- to 12-year-old children].

Movement-related brain potentials (MRBP) were recorded from F3, F4, C3, C4, and Cz in 47 children aged 9-10 and 49 children aged 11-12 in simple button-push task. Difference in MRBP parameters between the two groups was revealed. Amplitude of readiness potential in the left frontal derivation was higher in the older group than in the younger one. In the right frontal and central regions the readiness potential had definitive characteristics in both age groups. Two subcomponents (P2a and P2b) of P2 postmovement positivity were found in both groups. The amplitude of P2b subcomponent and the latency of N3 component increased from 9-10 to 11-12 years.

MeSH Terms

  • Aging
  • Brain
  • Child
  • Electroencephalography
  • Electrooculography
  • Humans
  • Longitudinal Studies
  • Membrane Potentials
  • Movement
  • Reaction Time
  • Time Factors
  • Twins, Dizygotic
  • Twins, Monozygotic


Decreased granulosa cell luteinizing hormone sensitivity and altered thecal estradiol concentration in the aged hen, Gallus domesticus.

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


Evaluation of right and left ventricular size in SHR-Wistar hybrids.

The relative right and left ventricular sizes were evaluated in hybrid rats obtained by crossing spontaneously hypertensive (SHR) and pure Wistar strains to detect cardiac hypertrophy dissociated from the hypertension genetically transmitted by the SHR strain. In female hybrids of the the F1, F2, and F3 generations, both ventricles were found to have bigger size in relation to body weight than in the pure Wistar, whereas only the F3 group was hypertensive. All generations of male hybrids had arterial pressure values in the hypertensive range, which were not consistently accompanied by increases in the ventricle mass. The correlation between arterial pressure and indexes of ventricular size was assessed in sex-age matched groups. In a range of systolic pressure values of 100-200 mmHg, the variables showed no correlation or poor positive correlation (correlation coefficient values from -0.3641 to 0.6153). The correlation was not improved in the F3 generation as would be expected, because these hybrids underwent higher left pressure load than the preceding generations. The results indicate that increased ventricular size in SHR-Wistar hybrids may be independent from the hypertension genetically transmitted by the SHR strain and suggest that some of the previously proposed factors, i.e., cardioadrenergic activity or the growth factor isolated from SHR hearts, may be playing a role in the ventricular hypertrophy process in this strain. If this characteristic of hybrids is a constant in pure SHR strain, its validity as a model of cardiac hypertrophy due to left pressure overload would be questioned.

MeSH Terms

  • Aging
  • Animals
  • Blood Pressure
  • Body Weight
  • Crosses, Genetic
  • Female
  • Heart Ventricles
  • Hybridization, Genetic
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred Strains
  • Sex Factors


Oligosaccharide composition, localization, and developmental changes of a CNS-specific (F3-87-8) glycoprotein.

The F3-87-8 glycoprotein was isolated from rat brain by immunoaffinity chromatography after biosynthetic labeling by intracerebral administration of [3H]glucosamine, and the oligosaccharide composition of pronase-derived glycopeptides was determined by sequential lectin affinity chromatography and alkali treatment. Triantennary complex oligosaccharides (65%) and O-glycosidic oligosaccharides (18%) were the predominant types present, accompanied by 7-10% each of biantennary and high-mannose oligosaccharides. Twenty-two percent of the complex oligosaccharides had a fucose residue linked to the proximal N-acetylglucosamine of the chitobiose units. No poly(N-acetyllactosaminyl) or hybrid oligosaccharides were detected. Immunocytochemical studies on the localization of this glycoprotein in developing rat brain demonstrated that in 1-week postnatal cerebellum, there is light staining of the internal granule cell layer and surrounding the Purkinje cells. By 2 weeks, an intense staining of myelinating fiber tracts appears, accompanied by much lighter staining in the granule cell layer and at the base of the molecular layer. Staining of the white matter remains strong at 3 weeks postnatal, together with significant staining throughout the molecular layer, and then decreases in both areas by 1 month. In adult brain there is relatively uniform staining of approximately equal intensity in the white matter, granule cell layer, and molecular layer, whereas the Purkinje cell bodies appear unstained throughout development. In agreement with a previously reported immunochemical analysis, no staining was seen in other tissues, confirming the CNS-specific localization of this glycoprotein.

MeSH Terms

  • Aging
  • Animals
  • Antibodies, Monoclonal
  • Brain
  • Brain Chemistry
  • Chromatography, Affinity
  • Glucosamine
  • Glycoproteins
  • Glycoside Hydrolases
  • Immunohistochemistry
  • Nerve Tissue Proteins
  • Oligosaccharides
  • Organ Specificity
  • Rats


Word-to-word variation in ERP component latencies: spoken words.

Data were collected shedding light on the brain electrical activity underlying word recognition. Subjects listened to a list of 48 spoken words in six random orders under two instructional sets: first to "think about the meanings of the words," and second, to learn the list. The scalp EEG associated with hearing and identifying the words was recorded at F3, F4, Cz, P3, P4, Pz, and Oz. Standard within-subjects time-locked averaging across words showed a late negative-positive complex with N2-P3 topography, the negative component peaking around 480 msec, the positive component peaking around 830 msec. Averaging within words across subjects uncovered considerable latency variability in both components. Within-word N2 and P3 component latencies covaried with word durations and with the "recognition points" predicted for the words by the "cohort theory" of word recognition. N2 latencies corresponded closely to the "N400" effect elicited with semantically incongruous sentence-final spoken words. Implications for ERP investigations of language processing are discussed.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Arousal
  • Attention
  • Cerebral Cortex
  • Electroencephalography
  • Evoked Potentials, Auditory
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phonetics
  • Reaction Time
  • Reference Values
  • Semantics
  • Sound Spectrography
  • Speech Perception


EEG and skeletal development in children with different psychosocial characteristics.

Two groups of children with different socioeconomic level were studied. One minute EEG at rest was recorded in monopolar leads F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5 and T6. Absolute and relative power in four EEg bands (delta, theta, alpha and beta) were computed. Radiographies of the left hand and the wrist were also obtained in all children. Age regression equations of the variables derived from EEG spectra were calculated in each group. In the group with low socioeconomic level many children had antecedents of risk factors. In this group absolute and relative power in the four bands presented a great dispersion and no correlation with age. In the group with good socioeconomic level the age regression equations of the EEG variables were significant, absolute values in the four bands decreased with age, as well as delta and theta relative power, while alpha and beta relative power increased with age. The area of the ossification center of each bone of the hand of the lower end of the ulna and radius were obtained from the X-ray film. Linear regression equations for the area of each ossification center were significant in both groups. No intercept or slope differences existed between both groups in any area. It is concluded that psychosocial disadvantage and antecedents of risk factors, although not producing any effect on skeletal development, do affect EEG maturation.

MeSH Terms

  • Adolescent
  • Aging
  • Bone Development
  • Child
  • Electroencephalography
  • Humans
  • Regression Analysis
  • Socioeconomic Factors


Development of the electroencephalographic rhythms of wakefulness in healthy infants during their first year.

Broad-band automated analysis was performed of the delta-, theta-, alpha- and beta EEG-rhythms from F3 and F4, C3, and C4, O1, and O2, T3 and T4 of healthy awake infants with open eyes. The data on the integrated amplitude of the above-mentioned rhythms were obtained in volt. sec. The age-determined changes in the mean values of this parameter were proved to be different in scope and in character. Generally speaking, the delta activity was not substantially changed in any of the areas indicated above at the end of the first year of life, compared with the first three months; the theta activity was substantially higher everywhere, with the exception of T3 and O2; the alpha activity was not increased only in T3 and T4, whereas the beta 1 activity was not increased in F3 and T3. Greatest changes were observed in the theta activity of the two central regions and O1, for the alpha activity--in the two occipital and the two central regions, for beta 1--generally in the right hemisphere. This state was attained predominantly through a gradual rise in the integrated amplitude of the respective rhythms, though there was also an abrupt development, mainly in the central and occipital regions.

MeSH Terms

  • Aging
  • Beta Rhythm
  • Delta Rhythm
  • Electroencephalography
  • Humans
  • Infant
  • Theta Rhythm
  • Wakefulness


Polymorphism of apolipoprotein A-II (apoA-II) among inbred strains of mice. Relationship between the molecular type of apoA-II and mouse senile amyloidosis.

Three types of apolipoprotein A-II (apoA-II) proteins (A, B and C) were predicted from the nucleotide sequence of apoA-II cDNA. Substitution of amino acid residues was noted at four positions (type A: Pro-5, Asp-20, Met-26, Ala-38; B: Pro-5, Glu-20, Val-26, Val-38; C: Gln-5, Glu-20, Val-26, Ala-38). Each type was identifiable by digestion of amplified apoA-II DNA by PCR, using restriction-fragment-length polymorphism of the apoA-II gene for restriction enzymes Cfr13I and MspI. The molecular type of apoA-II was determined among 23 strains of mice including nine of the senescence accelerated mouse series developed in our laboratory. Examination of types of apoA-II and amyloid deposition in the F2 and F3 hybrid mice showed that apoA-II amyloid deposition was present only in the mice homozygous for type C apoA-II and which were 12-17 months of age. The molecular type of apoA-II may be a factor involved in the development of senile amyloidosis in mice.

MeSH Terms

  • Aging
  • Amino Acid Sequence
  • Amyloidosis
  • Animals
  • Apolipoprotein A-II
  • Base Sequence
  • DNA
  • Hybridization, Genetic
  • Mice
  • Mice, Inbred A
  • Mice, Inbred AKR
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Mice, Inbred ICR
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Polymorphism, Restriction Fragment Length


[Age-related peculiarities of acetylation of rat liver nuclear histones].

The intensity of acetylation of different histone fraction is found to change in postnatal ontogenesis of albino rats. The intensity of acetylation of lisine-rich histone (F1) was maximal in 3-and 12-month old animals. The label incorporation into F3 (arginine-rich) histones considerably decreased in the time interval between 1st and 3d months while its incorporation increased into F2 histones furing all the period of postnatal development studied.

MeSH Terms

  • Acetylation
  • Aging
  • Animals
  • Arginine
  • Cell Nucleus
  • Histones
  • Liver
  • Lysine
  • Rats


Composition of liver histones in aging rat and mouse.

In contrast to the earlier reports on the age-dependent reduction of the ratio of F3 plus F2al plus F2a2 / Fl plus F2b in rat liver histones and the reduction of arginine-rich histone (F3 or III) in beef thymus, the result obtained by high-resolution polyacrylamide gel electrophoresis of histones shows no apparent age-related change in the proportion of any histone fraction of mouse and rat liver chromatin.

MeSH Terms

  • Aging
  • Animals
  • Cell Fractionation
  • Chromatin
  • Computers
  • Densitometry
  • Electrophoresis, Polyacrylamide Gel
  • Histones
  • Liver
  • Mice
  • Mice, Inbred C57BL
  • Rats
  • Rats, Inbred Strains
  • Spectrophotometry
  • Ultracentrifugation


Covalent modification of nuclear proteins during aging.

An in vitro assay system has been established to study acetylation and phosphorylation of nuclear proteins from isolated nuclei. Phosphorylation of neclear proteins reached a peak within 5 min while maximum acetylation occurred about 10 min later. The rate of acetylation of liver nuclear proteins in 15 min incubation was significantly higher in "old" mice (29 mo) than in "young" mice (2 mo), while there was no difference in phosphorylation. When nuclear histones were fractionated by polyacrylamide-urea electrophoresis the acetylation of histone F3 was increased in "old" mice to 129% and F2al to 112% of the values in "young" mice. Acetylation of phenol-soluble nuclear acidic proteins was increased to 250% and phosphorylation to 138% in "old" mice as compared to "young" mice. This increase in covalent modification of acidic proteins was found in tow specific fractions when separated by SDS-polyacrylamide gel electrophoresis. By contrast, the labeling of nucleoplasmic proteins, soluble in 0.14 M NaCl, showed no significant difference between the two ages.

MeSH Terms

  • Acetylation
  • Aging
  • Animals
  • Cell Nucleus
  • Cell Separation
  • Electrophoresis, Polyacrylamide Gel
  • Histones
  • Liver
  • Mice
  • Nucleoproteins
  • Phosphates


[Comparative study of microsomal enzymic activities in adult and foetal monkey hepatocytes (author's transl)].

Differential centrifugation was applied to adult and foetal liver of monkey. Obtained fractions were: F1 (800 X g); F2 (12 500 X g); F3 (200 000 X g); and cell sap. Analysis of chemical compounds of these fractions shows that: (1) adult and foetal nucleic acids levels are similar; (2) there are more proteins in adult than in foetal hepatocytes; (3) most of the glycogen is located in F3; the foetal level is twenty times higher than the adult level. Plasma membrane enzymes (5'-nucleotidase, adenylate cyclase) show a nucleomicrosomic distribution. The distribution of alkaline phosphatase is not significant. Mitochondrial enzymes (monoamine oxydase, succinate cytochrome c reductase, cytochrome oxydase) are enriched in F2 without any sedimentation in F3. There is more malate dehydrogenase liberated in cell sap during foetal liver fractionation. This indicates the foetal mitochondria are more sensitive to the homogenisation method. Lysosomal enzymes (acid phosphatase, N-acetylglucosaminidase) are enriched in F2. The same observation for N-acetylglucosaminidase as for malate dehydrogenase leads to the same conclusion for foetal lysosomes. Endoplasmic reticulum and Golgi enzymes (glucose-6-phosphatase and related phosphotransferase activity, NADPH-cytochrome c reductase and sialytransferase) are much enriched in F3. Thus this fraction F3 is pure enough to allow the observation of the modification produced on endoplasmic reticulum and Golgi apparatus during foetal and neonatal development.

MeSH Terms

  • Aging
  • Animals
  • Cell Fractionation
  • Cell Membrane
  • Cytoplasm
  • Erythrocebus patas
  • Female
  • Haplorhini
  • Liver
  • Microsomes, Liver
  • Mitochondria, Liver
  • Pregnancy