F2
Prothrombin precursor (EC 3.4.21.5) (Coagulation factor II) [Contains: Activation peptide fragment 1; Activation peptide fragment 2; Thrombin light chain; Thrombin heavy chain]
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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
Pollen-mediated gene flow of genetically modified crops to their wild relatives can facilitate the spread of transgenes into the ecosystem and alter the fitness of the consequential progeny. A two-year field study was conducted to quantify the gene flow from glufosinate-ammonium resistant (GR) soybean (Glycinemax) to its wild relative, wild soybean (G. soja), and assess the potential weed risk of hybrids resulting from the gene flow during their entire life cycle under field conditions in Korea, where wild soybean is the natural inhabitant. Pollen-mediated gene flow from GR soybeans to wild soybeans ranged from 0.292% (mixed planting) to 0.027% at 8 m distance. The log-logistic model described the gene flow rate with increasing distance from GR soybean to wild soybean; the estimated effective isolation distance for 0.01% gene flow between GR and wild soybeans was 37.7 m. The F1 and F2 hybrids exhibited the intermediate characteristics of their parental soybeans in their vegetative and reproductive stages. Canopy height and stem length of hybrids were close to those of wild soybean, which shows an indeterminate growth; the numbers of flowers, pods, and seeds per hybrid plant were close to those of wild soybean and significantly higher than those of GR soybean. Seed longevity of F2 hybrid plants was also intermediate but significantly greater than that of GR soybean due to high seed dormancy. Our results suggest that transgenes of the GR soybean might disperse into wild populations and persist in the agroecosystem of the genetic origin regions due to the pollen-mediated gene flow and the relatively high fitness of the hybrid progeny.
Keywords
- Glufosinate resistance
- Relative fitness
- Seed longevity
- Transgene flow
- Weed risk
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
Previous studies showed that gestational arsenite exposure increases incidence of hepatic tumors in the F1 and F2 male offspring in C3H mice. However, the mechanisms are largely unknown. In this study, we focused on whether cellular senescence and the senescence-associated secretory phenotype (SASP) contribute to tumor formation in C3H mice, and whether gestational arsenite exposure augments hepatic tumors through enhancement of cellular senescence. Three senescence markers (p16, p21 and p15) and two SASP factors (Cxcl1 and Mmp14) were increased in hepatic tumor tissues of 74- or 100-weeks-old C3H mice without arsenite exposure, and treatment with a senolytic drug (ABT-263) diminished hepatic tumor formation. Gestational arsenite exposure enhanced the expression of p16, p21 and Mmp14 in F1 and p15 and Cxcl1 in F2, respectively. Exploring the mechanisms by which arsenite exposure promotes cellular senescence, we found that the expression of antioxidant enzymes (Sod1 and Cat) were reduced in the tumors of F1 in the arsenite group, and Tgf-β and the receptors of Tgf-β were increased in the tumors of F2 in the arsenite group. Furthermore, the analysis of the Cancer Genome Atlas database showed that gene expression levels of the senescence markers and SASP factors were increased and associated with poor prognosis in human hepatocellular carcinoma (HCC). These results suggest that cellular senescence and SASP have important roles in hepatic tumorigenesis in C3H mice as well as HCC in humans, and gestational arsenite exposure of C3H mice enhances senescence in F1 and F2 via oxidative stress and Tgf-β activation, respectively.
Keywords
- Arsenic
- Liver
- Multigenerational Effect
- SASP
- Senescence
- Tumor
Longevity is associated with higher circulating levels of TSH in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown. We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels. We performed a case-control intervention study with a single intramuscular (gluteal) injection with 0.1 mg recombinant human TSH in a subgroup of 14 F2-LLS and 15 similarly aged F2-Con. They were followed for 4 days. No serious adverse events were reported. For analyses, we compared time trajectories of TSH and TH, and the ratio of TH to TSH using area under the curve (AUC) calculations. The AUC free T4/AUC TSH ratio was significantly lower in F2-LLS than in F2-Con (estimated mean [95% confidence interval] 1.6 [1.2-1.9] and 2.2 [1.9-2.6], respectively, P = 0.01). The AUC thyroglobulin/AUC TSH ratio was also lower in F2-LLS than in F2-Con (median [interquartile range] 2.1 [1.4-3.6] and 3.2 [2.7-7.4], respectively, P = 0.04). We observed the same trend with the AUC free T3/AUC TSH ratio, although the difference was not statistically significant (estimated mean [95% confidence interval] 0.6 [0.4-0.7] and 0.7 [0.6-0.8], respectively, P = 0.07). The present findings show that members of long-living families have a lower thyroid responsivity to TSH compared with their partners.
Keywords
- Thyroid
- longevity
- recombinant human TSH
- responsivity
Due to strain-specific behavioral idiosyncrasies, inbred mouse strains are suboptimal research models for behavioral aging studies. The aim of this study is to determine age-related behavioral changes of F2 hybrid C57BL/6NxBALB/c male and female mice. Lifespan was followed (n =48, n =51) and cohorts of mature adult (7 months), middle-aged (15 months), and old mice (22 months of age; n=7-12 per group) were assessed regarding open-field activity, exploration, passive avoidance learning/memory, and depressive-like behavior. We found that both males and females demonstrated decreased exploratory behavior with age, while memory and depressive-like behavior were maintained. Females exhibited enhanced depressive-like behavior compared to males; however, a correlation between fat mass and swimming activity in the test directly accounted for 30-46% of this behavioral sex difference. In addition, we suggest a method to qualitatively estimate natural lifespan from survival analyses in which animals with signs of pain or severe disease are euthanized. This is, to our knowledge, the first behavioral study to consider both sex and aging in hybrid mice. We here define decreased exploratory behavior as a conserved hallmark of aging independent of sex, highlight the effect of buoyancy in water tests, and provide a method to assay lifespan with reduced animal suffering.
MeSH Terms
- Adiposity
- Aging
- Animals
- Exploratory Behavior
- Female
- Male
- Memory
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Swimming
Keywords
- F2 hybrid mice
- aging
- exploratory activity
- sex comparison
- water-based behavioral tests
Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesic drugs, such as acetaminophen (APAP), are frequently taken during pregnancy, even in combination. However, they can favour genital malformations in newborn boys and reproductive disorders in adults. Conversely, the consequences on postnatal ovarian development and female reproductive health after in utero exposure are unknown. Here, we found that in mice, in utero exposure to therapeutic doses of the APAP-ibuprofen combination during sex determination led to delayed meiosis entry and progression in female F1 embryonic germ cells. Consequently, follicular activation was reduced in postnatal ovaries through the AKT/FOXO3 pathway, leading in F2 animals to subfertility, accelerated ovarian aging with abnormal corpus luteum persistence, due to decreased apoptosis and increased AKT-mediated luteal cell survival. Our study suggests that administration of these drugs during the critical period of sex determination could lead in humans to adverse effects that might be passed to the offspring.
MeSH Terms
- Acetaminophen
- Aging
- Animals
- Animals, Newborn
- Cell Proliferation
- Female
- Fertility
- Forkhead Box Protein O3
- Germ Cells
- Ibuprofen
- Luteolysis
- Mice
- Ovary
- Pregnancy
- Prenatal Exposure Delayed Effects
- Proto-Oncogene Proteins c-akt
- Reproduction
- Signal Transduction
Keywords
- Infertility
- Oogenesis
- Risk factors
The age-induced, exponential accumulation of mitochondrial DNA (mtDNA) deletion mutations contributes to muscle fiber loss. The causes of these mutations are not known. Systemic inflammation is associated with decreased muscle mass in older adults and is implicated in the formation of sporadic mtDNA deletions. Macrophage migration inhibitory factor knockout (MIF-KO) mice are long-lived with decreased inflammation. We hypothesized that aged MIF-KO mice would have lower mtDNA deletion frequencies and fewer electron transport chain (ETC) deficient fibers. We measured mtDNA copy number and mutation frequency as well as the number and length of ETC deficient fibers in 22-month old MIF-KO and F2 hybrid control mice. We also measured mtDNA copy number and deletion frequency in female UM-HET3 mice, a strain whose lifespan matches the MIF-KO mice. We did not observe a significant effect of MIF ablation on muscle mtDNA deletion frequency. There was a significantly lower mtDNA copy number in the MIF-KO mice and the lifespan-matched UM-HET3 mice compared to the F2 hybrids, suggesting the importance of genetic background in mtDNA copy number control. Our data do not support a definitive role for MIF in age-induced mtDNA deletions.
MeSH Terms
- Animals
- Cellular Senescence
- DNA Copy Number Variations
- DNA, Mitochondrial
- Intramolecular Oxidoreductases
- Longevity
- Macrophage Migration-Inhibitory Factors
- Macrophages
- Mice
- Mice, Knockout
Keywords
- Macrophage migration inhibitory factor
- Mitochondrial DNA
- Mutation
- Skeletal muscle
This study investigated the effect of zirconia surface treatment (air-abrasion with aluminum oxide or tribochemical silica coating) and aging on the fatigue behavior of thin monolithic Y-TZP (yttria-stabilized tetragonal zirconia polycrystal) restorations cemented with 2 types of resin cements, containing or not containing MDP, to a dentin-like substrate. Y-TZP ceramic (Zenostar T, diameter (Ø) 10 mm, 0.7 mm thick) and dentin-like discs (Ø 10 mm, 2.8 mm thick) were assigned into eight groups according to three factors: 'zirconia surface treatment' (aluminum oxide particles air-abrasion 'AO'; or tribochemical silica coating via silica-coated aluminum trioxide particles air-abrasion silanization 'SC'); 'MDP-containing resin cement' (with: Panavia F2.0, 'MDP'; or without: Multilink Automix, 'nMDP'); and 'aging' (baseline; or aged - 'AG':12,000 thermal cycles 60 days water storage). Y-TZP intaglio surface was conditioned and dentin-like substrate was etched with hydrofluoric acid prior to bonding. Aging was performed in half of the specimens before the fatigue testing (Staircase, 20 Hz; 250,000 cycles). Fractographic and topographic characteristics were analyzed by stereomicroscope and SEM. Prior to aging, no significant difference was found between the two surface treatments, irrespective to the cement. Samples bonded with resin cement containing MDP had a significant reduction in their fatigue failure load when Y-TZP was air-abraded with aluminum oxide particles and subjected to aging (MDP-AO = 2050.71 ; MDP-AO/AG = 1756.67 ). Other studied conditions were not affected by aging. Topographic images revealed a rougher surface for aluminum oxide air-abrasion. Fractography supports all failures as a radial crack starting at the Y-TZP intaglio surface. Bonded thin simplified Y-TZP restorations had a high load-bearing capacity, regardless of the studied factors. The MDP-containing resin cement applied on aluminum oxide air-abraded zirconia surface was not enough to maintain the fatigue performance after aging, while higher stability to aging was achieved by treating with the tribochemical silica coating method. When using MDP-free resin cement, the surface treatment and the aging did not impact the fatigue performance.
MeSH Terms
- Ceramics
- Dental Cements
- Dental Restoration Repair
- Dental Stress Analysis
- Materials Testing
- Resin Cements
- Silicon Dioxide
- Surface Properties
- Weight-Bearing
- Yttrium
- Zirconium
Keywords
- 10-methacryloyloxy-decyldihydrogen-phosphate
- Adhesion
- Fatigue behavior
- Interface aging
- Polycrystalline ceramics
- Sandblasting
A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer's Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation. The offspring was generated from females Senescence Accelerated Mouse-Prone (SAMP8) fed a resveratrol-enriched diet for two months prior to mating. Object novel recognition and Morris Water Maze (MWM) demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, [i]Dnmt3a/b[/i] and [i]Tet2[/i] gene expression changed. Methylation levels of [i]Nrf2[/i] and [i]NF-kβ[/i] genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring that resulted from a resveratrol fed mother showed increase AMPKα activation, mTOR inhibition, and an increase in [i]Pgc-1α[/i] gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways.
MeSH Terms
- Animals
- Antioxidants
- Cognitive Aging
- Cognitive Dysfunction
- DNA Methylation
- Female
- Hydrogen Peroxide
- Maternal-Fetal Exchange
- Maze Learning
- Mice
- Pregnancy
- Promoter Regions, Genetic
- Resveratrol
- Signal Transduction
Keywords
- NF-κB
- Nrf2
- SAMP8
- cognitive decline
- epigenetic inheritance
- epigenetics
- inflammation
- methylation
- oxidative stress
- resveratrol
Both inhibitory and stimulatory (known as hormesis) effects of the sublethal flupyradifurone, a butenolide insecticide, on Myzus persicae Sulzer (Hemiptera: Aphididae) were investigated for incorporating it into integrated pest management (IPM). A leaf-dip bioassay showed that flupyradifurone was very toxic against adult M. persicae with a 48 h LC50 of 8.491 mg/L. Using the age-stage two-sex life table approach, we assessed the effects of LC25 of flupyradifurone on adult M. persicae and its progeny (F1 and F2). On the one hand, aphids exposed to flupyradifurone had significantly negative effects on the life history traits acrossing the generations, such as reduced the adult longevity and fecundity of F0, shortened the duration of third instar and fourth instar nymphs, preadult period and the pre-reproductive period of F1, and decreased the reproductive days and adult longevity of F2. On the other hand, stimulatory effects on the duration of pre-adult, adult reproductive days, and reproduction of F1 were observed in the flupyradifurone-treated aphids. Consistently with the stimulation on individual traits, a higher net reproductive rate (R0) of F1 and a shorter mean generation time (T) of F2 were observed in the flupyradifurone-treated aphids, although the other population parameters including the intrinsic rate of increase (r), finite rate of increase (λ) and T of F1 and R0, r and λ of F2 were not significantly affected. These results revealed that adult M. persicae exposed to sublethal concentration of flupyradifurone can induce hormetic effects on F1, and also cause negative effects on F2. Our results would be useful for assessing the overall effects of flupyradifurone on M. persicae and the hormetic effects should take into consideration when use flupyradifurone for control M. persicae.
MeSH Terms
- 4-Butyrolactone
- Animals
- Aphids
- Fertility
- Hormesis
- Life Cycle Stages
- Longevity
- Prunus persica
- Pyridines
- Reproduction
Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs. We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs. Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1-0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4-0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019-3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated. Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Antiviral Agents
- Cost-Benefit Analysis
- HIV Infections
- Health Care Costs
- Hepacivirus
- Hepatitis C
- Humans
- Incidence
- Life Expectancy
- Male
- Middle Aged
- Models, Economic
- Netherlands
- Prevalence
- Quality-Adjusted Life Years
- Sexual and Gender Minorities
- Survival Rate
- Time Factors
- Time-to-Treatment
Addiction to drugs, including opioids is the result of an interplay between environmental and genetic factors. It has been shown that the progeny of addict people is at higher risk for drug addiction. However, the mechanisms of such trans-generational effects of drugs are not so clear. Here we have evaluated the effects of parental morphine consumption on anxiety, morphine preference, and mRNA expression of dopamine receptors in F1 and F2 male offspring. Morphine was chronically administered to adult male and female Wistar rats followed by 14-day abstinence before mating. Morphine preference and anxiety-like behavior in the offspring were measured by two-bottle-choice paradigm and elevated-plus maze, respectively. Real-time PCR was used to measure the mRNA expression level of dopamine receptors in the striatum, nucleus accumbens, prefrontal cortex, and hippocampus of F1 animals. The results indicated that F1 but not the F2 male progeny of morphine-exposed parents had a greater preference for morphine, and more anxiety-like behavior compared to the offspring of saline-treated parents. In F1 male progeny of morphine-treated parents, D1 and D5 dopamine receptors were significantly increased in the prefrontal cortex and nucleus accumbens. D5 and D2 receptors were decreased in the hippocampus. D4 dopamine receptor was augmented in striatum and hippocampus and decreased in the prefrontal cortex. Adulthood exposure to chronic morphine in male and female rats before conception leads to higher morphine preference and increased anxiety in F1 but not F2 male progeny. Alterations of dopamine receptor expression in the reward system may be one mechanism responsible for observed changes in F1 offspring.
MeSH Terms
- Aging
- Animals
- Anxiety
- Brain Chemistry
- Female
- Male
- Morphine
- Morphine Dependence
- Narcotics
- Pregnancy
- Rats
- Rats, Wistar
- Real-Time Polymerase Chain Reaction
- Receptors, Dopamine
- Reward
- Sex Characteristics
- Survival Analysis
Keywords
- Anxiety
- Dopamine receptor expression
- Morphine preference
- Offspring
The spinal column possesses shock absorption properties, mainly provided by the intervertebral discs. However, with the process of senescence, all structures of the spine, including the discs, undergo degenerative changes. It may lead to alteration of the mechanical properties of the spinal motion segment and diminished capacity for vibration attenuation. The objective of this study was to investigate the age-related changes in shock absorption properties of the spine. A total of 112 individuals divided into three groups according to age (third, fifth, and seventh decades of life) were enrolled in this study. The transmissibility of vibrations through the spine was measured in a standing position on a vibration platform by accelerometers mounted at the levels of S2 and C0. Registered signals were described using four parameters: VMS (variability), peak-to-peak amplitude (PPA), and spectral activity in two bands F2 (0.7-5 Hz) and F20 (15-25 Hz). In all age groups, signals registered at C0 were characterized by significantly lower values of VMS, PPA, and F20, when compared to level S2. Simultaneously, the parameter F20 significantly differed among all age groups when C0 vibrations were analyzed: 2.43±1.93, 5.02±3.61, and 10.84±5.12 for the third, fifth, and seventh decades of life, respectively. The human spinal column provides vibration attenuation; however, this property gradually declines with the aging process.
MeSH Terms
- Adult
- Aged
- Aging
- Female
- Healthy Volunteers
- Humans
- Intervertebral Disc
- Lumbar Vertebrae
- Male
- Middle Aged
- Posture
- Vibration
- Young Adult
Keywords
- amortization
- attenuation
- inter-vertebral disc
- senescence process
- vibration transmissibility
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
Psix saccharicola (Mani) (Hymenoptera: Platygastridae) is a solitary egg parasitoid of the pistachio green stink bug, Acrosternum arabicum (Wagner) (Hemiptera: Pentatomidae), which is one of the most important pests of pistachio in Iran. Augmentation of P. saccharicola field populations using mass-reared individuals may provide an alternative to conventional pesticide use for pistachio green stink bug control. Cold storage is an important component of mass-rearing protocols for optimum timing of host egg parasitization and potentially extended storage of P. saccharicola pupae prior to adult emergence. The impact of cold storage on A. arabicum eggs for various time intervals at 4.0°C was investigated. Results indicated that host eggs stored at 4.0°C for up to 60 d could be exploited by P. sacchricola, whereas no offspring were produced when eggs were stored for 120 d. The emergence rates of the F1 and F2 generations declined with increased host egg storage time. Both sex ratio and survival rate of the F2 generation decreased as the refrigeration time of host eggs increased. The impact of cold storage on P. saccharicola pupae was evaluated. Reared pupae of P. saccharicola were held for 1 wk at three temperatures and compared with a control (27 ± 1°C). Psix saccharicola pupae were tolerant to cold storage at 8 and 12°C. Cold storage adversely affected mean adult emergence at 4°C, which decreased following low temperature exposure. Furthermore, mean percentage survivorship was unaffected by storage at low temperatures in the F1 generation, but was reduced at 4°C. The sex ratio of the F1 generation became more male-biased when held at lower storage temperatures. The highest female proportion was observed at 12°C.
MeSH Terms
- Animals
- Body Size
- Cold Temperature
- Female
- Heteroptera
- Host-Parasite Interactions
- Life History Traits
- Longevity
- Male
- Ovum
- Pest Control, Biological
- Pupa
- Sex Ratio
- Wasps
Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity.
MeSH Terms
- Aging
- Animals
- Crosses, Genetic
- Dronabinol
- Female
- Inheritance Patterns
- Male
- Mice
- Motor Activity
- Phenotype
- Selection, Genetic
- Time Factors
Keywords
- Adolescent
- Cannabinoids
- Genetic
- Locomotion
- Selection
- THC
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
F2-isoprostanes (F2-isoPs) are biomarkers for oxidative stress in humans and have been shown to be elevated in obesity, cardiovascular disease, and diabetes. Therefore, F2-isoPs are often implicated in oxidative stress contributing to insulin resistance, although this has not been rigorously examined. To determine whether urinary F2-isoPs are predictive of insulin sensitivity and other clinical metabolic parameters. Sedentary, weight-stable, nondiabetic adults equilibrated on a standard isocaloric diet. Insulin sensitivity via hyperinsulinemic-euglycemic clamp, urinary F2-isoPs by gas chromatography-mass spectrometry, and body composition by dual-energy x-ray absorptiometry. No correlation was found between 15-F -IsoP nor its major metabolite, 2,3-dinor-5,6-dihydro-15-F -IsoP, with insulin sensitivity, even after adjusting for age, race, sex, BMI, and smoking status. 15-F -IsoP was also not associated with body fat. However, there was a strong negative correlation between 15-F -IsoP and lean body mass (LBM; r = -0.46, [i]P[/i] = 0.0001), bone mineral content (BMC; r = -0.58, [i]P[/i] < 0.0001), bone mineral density (BMD; r = -0.65, [i]P[/i] < 0.0001), and skeletal muscle protein 4-hydroxynonenal (4-HNE; r = -0.54, [i]P[/i] = 0.0239), another marker of oxidative stress. 15-F -IsoP was also positively associated with circulating triglycerides and total cholesterol, and increased as a function of age. Urinary 15-F -IsoP and its major metabolite are not associated with insulin sensitivity, suggesting the lipid peroxidation process that produces F2-isoPs does not reflect oxidative stress reactions operative in insulin resistance. However, urinary F2-isoPs were negatively correlated with LBM, BMC, BMD, and muscle 4-HNE. Because lean and bone mass decline as a function of biological aging, F2-isoPs may reflect the oxidative stress operative in the aging process.
Keywords
- F2-isoprostanes
- aging
- bone density
- insulin resistance
- lean body mass
- oxidative stress
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
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
Although genetic variations are heritable, some quantitative traits like longevity may have non-genomic influence on heritability. Laboratory-selected inbred strains of extended longevity phenotype of Drosophila offer an opportunity to study the inheritance of longevity. The aim of the study was to examine the heritability of longevity in an extended longevity phenotype of Drosophila melanogaster using reciprocal cross effects in F1 and F2 generations. Lifespan variations of virgin and mated flies in parent, F1 and F2 generations were investigated using reciprocal crosses between normal and long lifespan lines of inbred population of D. melanogaster. Heterosis, narrow-sense heritability, recombination loss, maternal effect and overdominance with respect to survivorship in virgin and mated flies were analyzed. Virgin flies lived longer than mated flies. There was no significant effect of mid-parent heterosis, recombination loss and overdominance on variations in longevity, whereas, significant maternal effect and narrow-sense heritability were observed in mated and virgin flies, respectively. Absence of heterosis in our study population of Drosophila phenotypes could be due to the lack of genetic heterogeneity. The heritability of the longevity trait in an inbred extended longevity phenotype depends on the variations in genetic and environmental factors.
MeSH Terms
- Animals
- Drosophila melanogaster
- Female
- Gene-Environment Interaction
- Genetic Variation
- Genotype
- Heredity
- Hybrid Vigor
- Longevity
- Male
- Phenotype
- Sex Factors
- Sexual Behavior, Animal
- Time Factors
Keywords
- Inbreeding depression
- epigenetics
- heterosis
- long lifespan
- maternal effect
- reciprocal cross
- virgin.
The endoparasitoid Microplitis prodeniae Rao and Chandry is an important potential augmentative biological control agent for lepidopteran pests of vegetables and tobacco. However, cold storage of pupae is required to ensure that sufficient parasitoids are available when they are needed in the field. In this study, pupae were maintained at 0, 4 or 10°C for 5-50 days after which the adults were evaluated for emergence, pre-emergence period, sex ratio, female longevity, oviposition period, and fecundity. Cold storage did not affect the pre-emergence period or proportion of females; however, there was a significant reduction in emergence, female longevity, oviposition period, and fecundity with increased exposure to cold. The pre-emergence period was approximately 5 days, and approximately 50% of the emergent parasitoids were females. A cold storage regime of 10 days at 10°C had no effect on the parasitoids and adult emergence was greater than 50% even after 20 days at 10°C. There was no carryover of the cold treatment from parental to F1 and F2 generations. Thus, M. prodeniae can be stockpiled for field release by exposing the pupae to a cold regime and subsequently holding them for adult emergence at 28°C.
MeSH Terms
- Animals
- Cold Temperature
- Female
- Fertility
- Longevity
- Male
- Pest Control, Biological
- Pupa
- Sex Ratio
- Spodoptera
- Wasps
Keywords
Microplitis prodeniae
- biological control
- cold storage
- emergence rate
- fecundity
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
This study sought to investigate the interaction of speech movement execution with higher order lexical parameters. The authors examined how lexical characteristics affect speech output in individuals with Parkinson's disease (PD) and healthy control (HC) speakers. Twenty speakers with PD and 12 healthy speakers read sentences with target words that varied in word frequency and neighborhood density. The formant transitions (F2 slopes) of the diphthongs in the target words were compared across lexical categories between PD and HC groups. Both groups of speakers produced steeper F2 slopes for the diphthongs in less frequent words and words from sparse neighborhoods. The magnitude of the increase in F2 slopes was significantly less in the PD than HC group. The lexical effect on the F2 slope differed among the diphthongs and between the 2 groups. PD and healthy speakers varied their acoustic output on the basis of word frequency and neighborhood density. F2 slope variations can be traced to higher level lexical differences. This lexical effect on articulation, however, appears to be constrained by PD.
MeSH Terms
- Adult
- Aged
- Aging
- Female
- Humans
- Linear Models
- Linguistics
- Male
- Middle Aged
- Motor Activity
- Parkinson Disease
- Speech
- Speech Production Measurement
Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively. Thus, PUFA improve the in vivo redox and oxidative stress induced aging process, which however does not exhibit a dose-dependent manner. Notably, both PUFA and fish oil effectively inactivated testicular telomerase and inhibited c-Myc-mediated telomerase reverse transcriptase expression, whereas n-3 PUFA rather than n-6 PUFA protected liver and testes against telomere shortening within the range of 13%-25% and 25%-27%, respectively. Therefore, n-3 PUFA may be better at inhibiting the DNA damage induced aging process. Surprisingly, only DHA significantly suppressed cellular senescence pathway evidenced by testicular antioncogene p16 and p53 expression. This work provides evident support for the crosstalk between PUFA especially n-3 PUFA and the aging process via maintaining the in vivo redox homeostasis, rescuing age-related telomere attrition and down-regulating the antioncogene expression.
MeSH Terms
- Age Factors
- Aging
- Animals
- Arachidonic Acid
- Brain
- Cellular Senescence
- DNA Damage
- Docosahexaenoic Acids
- Down-Regulation
- Genes, Tumor Suppressor
- Genes, p16
- Genes, p53
- Lipid Peroxidation
- Liver
- Male
- Mice, Inbred ICR
- Oxidation-Reduction
- Oxidative Stress
- Proto-Oncogene Proteins c-myc
- Signal Transduction
- Telomerase
- Telomere
- Telomere Homeostasis
- Telomere Shortening
- Testis
- Time Factors
Keywords
- Gerotarget
- anti-aging
- antioncogene
- polyunsaturated fatty acids
- redox
- telomere protection
- Statistical analyses in human populations have associated limited food availability during development with increased longevity of next generations. In support, recent findings in [i]Caenorhabditis elegans[/i] revealed nutritional effects on transgenerational longevity. : In this study we tested the effect of nutrition on longevity of future generations in [i]Drosophila[/i] and whether this is sex-specific. We reared male larvae and adults of [i]Drosophila[/i] under different food conditions and performed lifespan analyses in F2 generation. : Grandsons of males which experienced starvation through larval stages were long-lived and grandsons of well fed larvae were short lived, in two [i]Drosophila[/i] strains. In one strain, the nutritional effect on transgenerational longevity was transmitted through male line. Interestingly, we find that dietary restriction in adult males is the main nutritional condition affecting lifespan of grandsons. : Our findings suggest that nutritional regulation of transgenerational longevity is evolutionarily conserved and developmental stage - dependent in [i]Drosophila[/i].
Keywords
- Aging
- dietary restriction
- drosophila
- epigenetic regulation
- lifespan
- longevity
- starvation
- transgenerational inheritance
Transgenerational effects on health and development of early-life nutrition have gained increased attention recently. However, the underlying mechanisms of transgenerational transmission are only starting to emerge, with epigenetics as perhaps the most important mechanism. We recently reported the first animal model to study transgenerational programming of longevity after early-life dietary manipulations, enabling investigations to identify underlying epigenetic mechanisms. We report here that post-eclosion dietary manipulation (PDM) with a low-protein (LP) diet upregulates the protein level of E(z), an H3K27 specific methyltransferase, leading to higher levels of H3K27 trimethylation (H3K27me3). This PDM-mediated change in H3K27me3 corresponded with a shortened longevity of F0 flies as well as their F2 offspring. Specific RNAi-mediated post-eclosion knockdown of E(z) or pharmacological inhibition of its enzymatic function with EPZ-6438 in the F0 parents improved longevity while rendering H3K27me3 low across generations. Importantly, addition of EPZ-6438 to the LP diet fully alleviated the longevity-reducing effect of the LP PDM, supporting the increased level of E(z)-dependent H3K27me3 as the primary cause and immediate early-life period as the critical time to program longevity through epigenetic regulation. These observations establish E(z)-mediated H3K27me3 as one epigenetic mechanism underlying nutritional programming of longevity and support the use of EPZ-6438 to extend lifespan.
MeSH Terms
- Animals
- DNA Methylation
- Diet
- Dietary Proteins
- Drosophila melanogaster
- Histones
- Longevity
- RNA Interference
Keywords
- E(z)
- H3K27me3
- longevity
- nutritional programming
- transgenerational inheritance
To evaluate a potential correlation between flexural strength and indirect tensile strength in assessing the mechanical strength of resin composite cements. Flexural strength (n = 5) and indirect tensile strength (n = 5) of 7 resin composite cements (RelyX Unicem 2 Automix [RXU], Panavia SA [PSA], Clearfil SA [CSA], Panavia F2.0 [PF2], Multilink Implant [MLI], DuoCem [DCM], Panavia 21 [P21]) were determined. Specimens were either auto-polymerized or dual-cured (except P21) and stored in water at 37 °C for 1 day prior to measurement. Flexural and indirect tensile strength of 4 cements (RXU, PSA, PF2, MLI) was additionally measured directly after curing and after 96 h water storage at 37 °C. Except for PF2, dual-cured specimens achieved higher flexural strength than auto-polymerized specimens. In the indirect tensile strength test differences in auto-polymerized and dual-cured specimens were only detected for RXU and DCM. A general non-linear correlation was found between flexural and indirect tensile strength values. However, strength values of auto-polymerized and dual-cured specimens did not generally correlate. Flexural strength and indirect tensile strength of resin composite cements are correlated. At high strength values the indirect tensile test is less sensitive than the flexural test. The results suggest that the indirect tensile test may only be recommended as a screening test especially for low or medium strength resin composite cements.
MeSH Terms
- Composite Resins
- Dental Stress Analysis
- Humans
- Materials Testing
- Phosphates
- Resin Cements
- Sensitivity and Specificity
- Tensile Strength
Keywords
- Aging
- Auto-polymerizing cement
- Curing mode
- Dual-curing cement
- Flexural strength
- Indirect tensile strength
- Resin composite cement
The effects of aging and freezing/thawing sequence on color, physicochemical, and enzymatic characteristics of two beef muscles ([i]Mm. gluteus medius[/i], GM and [i]biceps femoris[/i], BF) were evaluated. Beef muscles at 3 d postmortem were assigned to four different combinations of aging and freezing/thawing sequence as follows; aging at 2°C for 3 wk (A3, never-frozen control), freezing at -28°C for 2 wk then thawing (F2, frozen/thawed-only), aging at 2°C for 3 wk, freezing at -28°C for 2 wk then thawing (A3F2), and freezing at -28°C for 2 wk, thawing then further aging at 2°C for 3 wk (F2A3). No significant interactions between different aging/freezing/thawing treatments and muscle type on all measurements were found. Postmortem aging, regardless of aging/freezing/thawing sequence, had no impact on color stability of frozen/thawed beef muscles (p<0.05). F2A3 resulted in higher purge loss than F2 and A3F2 treatments (p<0.05). A3F2 and F2A3 treatments resulted in lower shear force of beef muscles compared to F2 (p<0.05). Although there was no significant difference in glutathione peroxidase (GSH-Px) activity, F2A3 had the highest β-N-acetyl glucominidase (BNAG) activity in purge, but the lowest BNAG activity in muscle (p<0.05). GM muscle exhibited higher total color changes and purge loss, and lower GSH-Px activity than BF muscle. The results from this present study indicate that different combinations of aging/freezing/thawing sequence would result in considerable impacts on meat quality attributes, particularly thaw/purge loss and tenderness. Developing a novel freezing strategy combined with postmortem aging will be beneficial for the food/meat industry to maximize its positive impacts on tenderness, while minimizing thaw/purge loss of frozen/thawed meat.
Keywords
- Aging
- Freezing
- Glutathione Peroxidase
- Purge
- Thawing
Neurodegenerative diseases and chronic cigarette smoking are associated with increased cerebral oxidative stress (OxS). Elevated F2-isoprostane levels in biological fluid is a recognized marker of OxS. This study assessed the association of active cigarette smoking with F2-isoprostane in concentrations in cognitively-normal elders (CN), and those with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD). Smoking and non-smoking CN (n = 83), MCI (n = 164), and probable AD (n = 101) were compared on cerebrospinal fluid (CSF) iPF2α-III and 8,12, iso-iPF2α-VI F2-isoprostane concentrations. Associations between F2-isoprostane levels and hippocampal volumes were also evaluated. In CN and AD, smokers had higher iPF2α-III concentration; overall, smoking AD showed the highest iPF2α-III concentration across groups. Smoking and non-smoking MCI did not differ on iPF2α-III concentration. No group differences were apparent on 8,12, iso-iPF2α-VI concentration, but across AD, higher 8,12, iso-iPF2α-VI level was related to smaller left and total hippocampal volumes. Results indicate that active cigarette smoking in CN and probable AD is associated with increased central nervous system OxS. Further investigation of factors mediating/moderating the absence of smoking effects on CSF F2-isoprostane levels in MCI is warranted. In AD, increasing magnitude of OxS appeared to be related to smaller hippocampal volume. This study contributes additional novel information to the mounting body of evidence that cigarette smoking is associated with adverse effects on the human central nervous system across the lifespan.
MeSH Terms
- Aged
- Aging
- Alzheimer Disease
- Biomarkers
- Cigarette Smoking
- Cognitive Dysfunction
- Female
- Hippocampus
- Humans
- Male
- Organ Size
- Oxidative Stress
Keywords
- Alzheimer’s disease
- F2-isoprostanes
- cigarette smoking
- hippocampus
- mild cognitive impairment
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
The results of recent studies have provided strong evidence for the transgenerational effects of parental exposure to ionising radiation and chemical mutagens. However, the transgenerational effects of parental exposure on survival and fertility remain poorly understood. To establish whether parental irradiation can affect the survival and fertility of directly exposed organisms and their offspring, crustacean Daphnia magna were given 10, 100, 1000 and 10,000mGy of acute γ-rays. Exposure to 1000 and 10,000mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. The fertility of F0 and F1Daphnia gradually declined with the dose of parental exposure and significantly decreased at dose of 100mGy and at higher doses. The effects of parental irradiation on the number of broods were only observed among the F0Daphnia exposed to 1000 and 10,000mGy, whereas the brood size was equally affected in the two consecutive generations. In contrast, the F2 total fertility was compromised only among progeny of parents that received the highest dose of 10,000mGy. We propose that the decreased fertility observed among the F2 progeny of parents exposed to 10,000mGy is attributed to transgenerational effects of parental irradiation. Our results also indicate a substantial recovery of the F2 progeny of irradiated F0Daphnia exposed to the lower doses of acute γ-rays.
MeSH Terms
- Animals
- Daphnia
- Fertility
- Gamma Rays
- Longevity
Keywords
- Daphnia
- Fertility
- Radiation
- Transgenerational
- Viability
Schizophrenia is one of the most disabling psychiatric disorders with increased morbidity and mortality. Both schizophrenia and oxidative stress have been associated with accelerated aging. Previous studies found increased oxidative stress in individuals with schizophrenia, though only one study measured F2-isoprostanes and did so in urine. To our knowledge, the present study is the first to assess plasma F2-isoprostane levels, the putative gold standard measure of systemic oxidative stress in vivo, in schizophrenia. We compared plasma F2-isoprostane levels in 134 stable outpatients with schizophrenia and 120 age- and gender-matched healthy comparison (HC) subjects. Sociodemographic and clinical data were collected in both groups. Plasma F2-isoprostane levels were significantly higher in the schizophrenia group than in the HC group. Women had higher F2-isoprostane levels compared to men, and those with higher body mass index (BMI) had higher levels, within each group. F2-isoprostane levels correlated with BMI, physical functioning, and medical comorbidity but not with severity of psychopathology or executive function. Linear models showed significant effects of diagnosis, gender, and BMI on F2-isoprostane levels, but no interactions. Our finding of increased oxidative stress in schizophrenia is consistent with reports of increased morbidity and mortality as well as accelerated aging in schizophrenia. The significant associations between F2-isoprostane levels and both gender and BMI warrant further study.
MeSH Terms
- Adult
- Aged
- Aging
- Biomarkers
- Body Mass Index
- Cross-Sectional Studies
- F2-Isoprostanes
- Female
- Humans
- Male
- Middle Aged
- Oxidative Stress
- Psychotic Disorders
- Schizophrenia
Keywords
- Aging
- Body mass index
- F2-isoprostanes
- Gender
- Oxidative stress
- Schizophrenia
Wnt5a and Mrfzb1 genes are involved in the regulation of tooth size, and their expression levels are similar to that of Bmp7 during morphogenesis, including during the cap and early bell stages of tooth formation. We previously reported that Usag-1-deficient mice form supernumerary maxillary incisors. Thus, we hypothesized that BMP7 and USAG-1 signaling molecules may play important roles in tooth morphogenesis. In this study, we established double genetically modified mice to examine the in vivo inter-relationships between Bmp7 and Usag-1. We measured the volume and cross-sectional areas of the mandibular incisors using micro-computed tomography (micro-CT) in adult Bmp7- and Usag-1-LacZ knock-in mice and their F2 generation upon interbreeding. The mandibular incisors of adult Bmp7 /- mice were significantly larger than those of wild-type (WT) mice. The mandibular incisors of adult Usag-1-/- mice were the largest of all genotypes examined. In the F2 generation, the effects of these genes were additive; Bmp7 /- was most strongly associated with the increase in tooth size using generalized linear models, and the total area of mandibular supernumerary incisors of Usag-1-/-Bmp7 /- mice was significantly larger than that of Usag-1-/-Bmp7 / mice. At embryonic day 15 (E15), BrdU assays demonstrated that the labeling index of Bmp7 /- embryos was significantly higher than that of WT embryos in the cervical loop. Additionally, the labeling index of Usag-1-/- embryos was significantly the highest of all genotypes examined in dental papilla. Bmp7 heterozygous mice exhibited significantly increased tooth sizes, suggesting that tooth size was controlled by specific gene expression. Our findings may be useful in applications of regenerative medicine and dentistry.
MeSH Terms
- Adaptor Proteins, Signal Transducing
- Aging
- Animals
- Apoptosis
- Bone Morphogenetic Protein 7
- Bone Morphogenetic Proteins
- Bromodeoxyuridine
- Cell Proliferation
- Crosses, Genetic
- Embryo, Mammalian
- Female
- Gene Expression Regulation, Developmental
- Gene Knock-In Techniques
- In Situ Nick-End Labeling
- Incisor
- Linear Models
- Male
- Mandible
- Mice, Inbred C57BL
- Molar
- Morphogenesis
- Organ Size
- Phenotype
- Staining and Labeling
- Tooth
- X-Ray Microtomography
- beta-Galactosidase
Keywords
- Bmp7
- Mouse model
- Tooth morphogenesis
- Tooth size
- Tooth volume
- Usag-1
The early-life environment, in particular maternal diet during pregnancy, influences a wide range of organs and systems in adult offspring. Mounting evidence suggests that developmental programming can also influence health and disease in grand-offspring. Transgenerational effects can be defined as those persisting into an F2 generation, where the F0 mother experiences suboptimal diet during her pregnancy. In this review, we critically examine evidence for transgenerational developmental programming effects in human populations, focusing on metabolic and reproductive outcomes. We discuss evidence from historical cohorts suggesting that grandchildren of women exposed to famine and other dietary alterations during pregnancy may experience increased rates of later health complications than their control counterparts. The methodological difficulties with transgenerational studies in human cohorts are explored. In particular, the problems with assessing reproductive outcomes in human populations are discussed. In light of the relative paucity of evidence available from human cohorts, we consider key insights from transgenerational experimental animal models of developmental programming by maternal diet; data are drawn from a range of rodent models, as well as the guinea-pig and the sheep. The evidence for different potential mechanisms of transgenerational inheritance or re-propagation of developmental programming effects is evaluated. Transgenerational effects could be transmitted through methylation of the gametes via the paternal and maternal lineage, as well as other possible mechanisms via the maternal lineage. Finally, future directions for exploring these underlying mechanisms further are proposed, including utilizing large, well-characterized, prospective pregnancy cohorts that include biobanks, which have been established in various populations during the last few decades.
MeSH Terms
- Aging
- Animals
- Epigenesis, Genetic
- Female
- Guinea Pigs
- Humans
- Maternal Inheritance
- Pregnancy
- Prenatal Exposure Delayed Effects
- Sheep
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
Huntington's disease is induced by CAG expansion in a single gene coding the huntingtin protein. The mutated huntingtin (mtHtt) primarily causes degeneration of neurons in the brain, but it also affects peripheral tissues, including testes. We studied sperm and testes of transgenic boars expressing the N-terminal region of human mtHtt. In this study, measures of reproductive parameters and electron microscopy (EM) images of spermatozoa and testes of transgenic (TgHD) and wild-type (WT) boars of F1 (24-48 months old) and F2 (12-36 months old) generations were compared. In addition, immunofluorescence, immunohistochemistry, Western blot, hormonal analysis and whole-genome sequencing were done in order to elucidate the effects of mtHtt. Evidence for fertility failure of both TgHD generations was observed at the age of 13 months. Reproductive parameters declined and progressively worsened with age. EM revealed numerous pathological features in sperm tails and in testicular epithelium from 24- and 36-month-old TgHD boars. Moreover, immunohistochemistry confirmed significantly lower proliferation activity of spermatogonia in transgenic testes. mtHtt was highly expressed in spermatozoa and testes of TgHD boars and localized in all cells of seminiferous tubules. Levels of fertility-related hormones did not differ in TgHD and WT siblings. Genome analysis confirmed that insertion of the lentiviral construct did not interrupt any coding sequence in the pig genome. The sperm and testicular degeneration of TgHD boars is caused by gain-of-function of the highly expressed mtHtt.
MeSH Terms
- Aging
- Animals
- Animals, Genetically Modified
- Cell Proliferation
- Disease Models, Animal
- Genetic Vectors
- Humans
- Huntingtin Protein
- Huntington Disease
- Lentivirus
- Male
- Mutation
- Sperm Count
- Spermatozoa
- Swine
- Swine, Miniature
- Testis
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
Nysius natalensis Evans (Hemiptera: Orsillidae) is a pest of sunflower in South Africa. Adults invade sunflower fields from their weedy hosts. The host plant suitability for development and survival and the effect of between-generation host switching were studied on different wild host plants and sunflower. Parameters used to assess host plant suitability were nymphal development, head widths, mean mass, and survival. Nymphs and adults were provided with crushed seed of five host plants, as well as a combination of seeds of the five species. Duration of the nymphal stage, development and mortality, and mean development time to adult were recorded. Between-generation host switching was studied by providing first-instar nymphs (F2) with seed of either the same plant species or transferred to different ones. Mean mass and mean head widths of adults (F2) were determined. The food source during the first and second generation, as well as the interaction thereof, has a significant effect on head widths of resultant males and females, as well as on female mass, but first-generation food did not have a significant effect on male mass. Feeding the F2 on sunflower proved to be beneficial to the false chinch bug, as it provided the heaviest males and females as well as females with the biggest head widths. Lack of constant availability of moisture had a detrimental effect on longevity. Host plant switching to sunflower likely happens as a result of senescence of wild host plants prior to winter.
MeSH Terms
- Animal Nutritional Physiological Phenomena
- Animals
- Body Weight
- Female
- Head
- Helianthus
- Heteroptera
- Longevity
- Male
- Nymph
- Plant Weeds
- Sex Factors
- South Africa
- Water Deprivation
Keywords
- Nysius natalensis
- cultural control
- development
- host switching
- sunflower
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
Contrasting data exist on the effect of gender and menopause on the susceptibility, development and liver damage progression in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether menopause is associated with the severity of liver fibrosis in individuals with NAFLD and to explore the issue of ovarian senescence in experimental liver steatosis in zebrafish. In 244 females and age-matched males with biopsy-proven NAFLD, we assessed anthropometric, biochemical and metabolic features, including menopausal status (self-reported); liver biopsy was scored according to 'The Pathology Committee of the NASH Clinical Research Network'. Young and old male and female zebrafish were fed for 24 weeks with a high-calorie diet. Weekly body mass index (BMI), histopathological examination and quantitative real-time PCR analysis on genes involved in lipid metabolism, inflammation and fibrosis were performed. In the entire cohort, at multivariate logistic regression, male gender [odds ratio (OR): 1.408, 95% confidence interval (95% CI): 0.779-2.542, P=0.25] vs women at reproductive age was not associated with F2-F4 fibrosis, whereas a trend was observed for menopause (OR: 1.752, 95% CI: 0.956-3.208, P=0.06). In women, menopause (OR: 2.717, 95% CI: 1.020-7.237, P=0.04) was independently associated with F2-F4 fibrosis. Similarly, in overfed zebrafish, old female fish with failing ovarian function [as demonstrated by extremely low circulating estradiol levels (1.4±0.1 pg/µl) and prevailing presence of atretic follicles in the ovaries] developed massive steatosis and substantial fibrosis (comparable with that occurring in males), whereas young female fish developed less steatosis and were totally protected from the development of fibrosis. Ovarian senescence significantly increases the risk of fibrosis severity both in humans with NAFLD and in zebrafish with experimental steatosis.
MeSH Terms
- Adult
- Aged
- Animals
- Anthropometry
- Biopsy
- Body Mass Index
- Cellular Senescence
- Cohort Studies
- Disease Progression
- Female
- Humans
- Liver Cirrhosis
- Male
- Menopause
- Middle Aged
- Models, Animal
- Non-alcoholic Fatty Liver Disease
- Odds Ratio
- Ovary
- Real-Time Polymerase Chain Reaction
- Risk Factors
- Zebrafish
Keywords
- Fibrosis
- Menopause
- Non-alcoholic fatty liver disease
- Ovarian senescence
- Zebrafish
Mortality is a highly complex trait influenced by a wide array of genetic factors. We examined a population of 1200 mice that were F2 generation offspring of a 4-way reciprocal cross between C57BL6/J and DBA2/J strains. Animals were sacrificed at age 200, 500, or 800 days and genotyped at 96 markers. The 800 days old cohort, which were the survivors of a much larger breeding group, were examined for enriched frequency of alleles that benefit survival and depletion of alleles that reduce survival. Loci on Chr 13 in males and on Chr X in females were significantly distorted from Mendelian expectations, even after conservative correction for multiple testing. DBA2/J alleles between 35 and 80 Mb on Chr 13 were underrepresented in the age 800 male animals. D2 genotypes in this region were also associated with premature death during behavioral testing. Furthermore, confirmatory analysis showed BXD recombinant inbred strains carrying the D2 alleles in this region had shorter median survival. Exploration of available pathology data indicated that a syndrome involving dental malocclusions, pancreatic islet hypertrophy, and kidney lipidosis may have mediated the effects of DBA alleles on mortality specifically in male mice. The heterozygote advantage locus on the X Chr was not found to be associated with any pathology. These results suggest a novel locus influencing survival in the B6/D2 genetic background, perhaps via a metabolic disorder that emerges by 200 days of age in male animals.
MeSH Terms
- Alleles
- Animals
- Chromosomes, Mammalian
- Female
- Genetic Linkage
- Longevity
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Inbred DBA
Keywords
- Lifespan
- Linkage
- Longevity
- Mouse
- Pathology
The aim of the investigation was to contribute to the ongoing discussion at the international standardization committee on how to artificially age dental resin composite cements. Indirect tensile strength (n=30) of a dual-cured resin composite cement (Panavia F2.0) was measured to evaluate the effect of water storage at 37°C or thermal cycling (5°C/55°C/1min) for up to 64 days. The influence of water temperature (5-65°C) after 16 days and the effect of 1 day water storage at 37°C prior to aging were assessed. Storage in air at 37°C served as control. Thermal cycling affected the indirect tensile strength most, followed by water storage at 55°C, whereas water storage at 37°C had only little influence. Major deterioration occurred before day 4 (≈6000 cycles). A 1-day pre-treatment by water storage at 37°C prior to thermal cycling attenuated the effect of aging. For the material investigated, thermal cycling for 4 days is the most efficient aging procedure. A 1-day water storage at 37°C prior to thermal cycling is recommended to allow complete polymerization. A 4-day water storage at 55°C may be considered as a viable alternative to thermal cycling.
MeSH Terms
- Acrylic Resins
- Adhesiveness
- Composite Resins
- Dental Stress Analysis
- Hardness
- Materials Testing
- Polyurethanes
- Surface Properties
- Temperature
- Tensile Strength
- Time Factors
- Water
Keywords
- Aging
- Compressive strength
- Indirect tensile strength
- International standardization
- Resin composite cement
- Thermal cycling
Our previous studies showed that adult (8 month) mice lacking CuZn-superoxide dismutase (CuZnSOD, Sod1KO mice) have neuromuscular changes resulting in dramatic accelerated muscle atrophy and weakness that mimics age-related sarcopenia. We have further shown that loss of CuZnSOD targeted to skeletal muscle alone results in only mild weakness and no muscle atrophy. In this study, we targeted deletion of CuZnSOD specifically to neurons (nSod1KO mice) and determined the effect on muscle mass and weakness. The nSod1KO mice show a significant loss of CuZnSOD activity and protein level in brain and spinal cord but not in muscle tissue. The masses of the gastrocnemius, tibialis anterior and extensor digitorum longus (EDL) muscles were not reduced in nSod1KO compared to wild type mice, even at 20 months of age, although the quadriceps and soleus muscles showed small but statistically significant reductions in mass in the nSod1KO mice. Maximum isometric specific force was reduced by 8-10% in the gastrocnemius and EDL muscle of nSod1KO mice, while soleus was not affected. Muscle mitochondrial ROS generation and oxidative stress measured by levels of reactive oxygen/nitrogen species (RONS) regulatory enzymes, protein nitration and F2-isoprostane levels were not increased in muscle from the nSod1KO mice. Although we did not find evidence of denervation in the nSod1KO mice, neuromuscular junction morphology was altered and the expression of genes associated with denervation acetylcholine receptor subunit alpha (AChRα), the transcription factor, Runx1 and GADD45α) was increased, supporting a role for neuronal loss of CuZnSOD initiating alterations at the neuromuscular junction. These results and our previous studies support the concept that CuZnSOD deficits in either the motor neuron or muscle alone are not sufficient to initiate a full sarcopenic phenotype and that deficits in both tissues are required to recapitulate the loss of muscle observed in Sod1KO mice.
MeSH Terms
- Aging
- Animals
- Cell Cycle Proteins
- Core Binding Factor Alpha 2 Subunit
- F2-Isoprostanes
- Gas Chromatography-Mass Spectrometry
- Mice
- Mice, Knockout
- Microscopy, Fluorescence
- Mitochondria
- Muscle, Skeletal
- Neuromuscular Junction
- Neurons
- Nuclear Proteins
- Oxidative Stress
- Phenotype
- Reactive Nitrogen Species
- Reactive Oxygen Species
- Receptors, Cholinergic
- Sarcopenia
- Superoxide Dismutase
Keywords
- CuZnSOD
- Muscle atrophy
- Neuromuscular junction
- Oxidative stress
- Sarcopenia
Low birth weight, due to uteroplacental insufficiency, results in programmed bone deficits in the first generation (F1). These deficits may be passed onto subsequent generations. We characterized the effects of being born small on maternal bone health during pregnancy; and aimed to characterize the contribution of the maternal environment and germ line effects to bone health in F2 offspring from mothers born small. Bilateral uterine vessel ligation (or sham) surgery was performed on female F0 WKY rats on gestational day 18 (term 22days) to induce uteroplacental insufficiency and fetal growth restriction. Control and Restricted F1 female offspring were allocated to a non-pregnant or pregnant group. To generate F2 offspring, F1 females were allocated to either non-embryo or embryo transfer groups. Embryo transfer was performed on gestational day 1, where second generation (F2) embryos were gestated (donor-in-recipient) in either a Control (Control-in-Control, Restricted-in-Control) or Restricted (Control-in-Restricted, Restricted-in-Restricted) mother. Restricted F1 females were born 10-15% lighter than Controls. Restricted non-pregnant females had shorter femurs, reduced trabecular and cortical bone mineral contents, trabecular density and bone geometry measures determined by peripheral quantitative computed tomography (pQCT) compared to non-pregnant Controls. Pregnancy restored the bone deficits that were present in F1 Restricted females. F2 non-embryo transfer male and female offspring were born of normal weight, while F2 embryo transfer males and females gestated in a Control mother (Control-in-Control, Restricted-in-Control) were heavier at birth compared to offspring gestated in a Restricted mother (Restricted-in-Restricted, Control-in-Restricted). Male F2 Restricted embryo groups (Restricted-in-Control and Restricted-in-Restricted) had accelerated postnatal growth. There was no transmission of bone deficits present at 35days or 6months in F2 offspring. Embryo transfer procedure had confounding effects preventing the separation of maternal environment and germ line contribution to outcomes. Deficits present in F1 non-pregnant Restricted females were absent during late gestation, indicating that pregnant F1 Restricted females experienced gains in bone. These beneficial maternal pregnancy adaptations may have prevented transmission of bone deficits to F2 offspring.
MeSH Terms
- Aging
- Animals
- Body Weight
- Bone Density
- Bone and Bones
- Crosses, Genetic
- Embryo Transfer
- Female
- Femur
- Fetal Growth Retardation
- Male
- Pregnancy
- Rats, Inbred WKY
- Tomography, X-Ray Computed
Keywords
- Bone
- Embryo transfer
- Growth restriction
- Pregnancy
- pQCT
Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1( ) bigenic mice with SVCT2( /-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2( /-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2( /-) and APP/PSEN1( ) mice and the combination genotype SVCT2( /-)APP/PSEN1( ) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2( /-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2( /-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2( /-)APP/PSEN1( ) mice compared to APP/PSEN1( ) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.
MeSH Terms
- Aging
- Alzheimer Disease
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Animals
- Anxiety
- Ascorbic Acid
- Ascorbic Acid Deficiency
- Brain
- Cognition Disorders
- Disease Models, Animal
- Female
- Learning
- Male
- Memory
- Mice, Transgenic
- Motor Activity
- Oxidative Stress
- Peptide Fragments
- Presenilin-1
- Sodium-Coupled Vitamin C Transporters
Keywords
- Alzheimer’s disease
- Vitamin C
- amyloid
- cognition
- mouse models
- oxidative stress
Cut-off points (COPs) for appendicular lean mass (ALM) index, essential to define low muscle mass (LMM) in the elderly, have never been officially defined for Poland. The aim of the study was to establish them. Additionally, the significance of body mass index (BMI) for correctly defining the COPs in a young, healthy reference group was assessed. The study was composed of reference group (n = 1113) and the elderly group (n = 200). In all subjects, body composition was assessed by bioimpedance analysis, and ALM index was calculated. Next, COPs (kg/m(2)) were set up for the whole reference group and for particular subgroups with different BMIs separately. They were used to diagnose sarcopenia in the elderly. COP for all young females was 5.37 (COP-F), while it was equal to 5.52 (COP-F2) when only those with a recommended BMI (18.50-24.99 kg/m(2)) were taken into consideration. For males, it was 7.32 and 7.29, respectively. Only 7% of elderly females had LMM based on COP-F and 15% had LMM based on COP-F2 (P < 0.05); for males, the percentages were 18% and 16%, respectively. COPs for LMM for Poland are 5.52 kg/m(2) (females) and 7.29 kg/m(2) (males). The reference group BMI is an important factor in establishing COPs for low muscle mass.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Body Mass Index
- Bone Density
- Female
- Humans
- Male
- Muscle, Skeletal
- Poland
A single bout of acute exercise increases oxidative stress and stimulates a transient increase in antioxidant enzymes. We asked whether this response would induce protection from a subsequent oxidative challenge, different from that of exercise, and whether the effects were affected by aging. We compared young (20 ± 1 years, n = 8) and older (58 ± 6 years, n = 9) healthy men and women. Resistance to oxidative stress was measured by the F2-isoprostane response to forearm ischemia/reperfusion (I/R) trial. Each participant underwent the I/R trial twice, in random order; once after performing 45 min of cycling on the preceding day (IRX) and a control trial without any physical activity (IRC). Baseline F2-isoprostane levels were significantly lower at IRX compared to IRC (P < 0.05) and not different between groups. F2-isoprostane response to IRX was significantly lower compared to IRC in young (P < 0.05) but not different in the older group. Superoxide dismutase activity in response to acute exercise was significantly higher in young compared to older adults (P < 0.05). These data suggest that signal transduction of acute exercise may be impaired with aging. Repeated bouts of transient reactive oxygen species production as seen with regular exercise may be needed to increase resistance to oxidative stress in older individuals.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aging
- Analysis of Variance
- Antioxidants
- Arm
- Biomarkers
- Cross-Over Studies
- Exercise
- Exercise Test
- F2-Isoprostanes
- Female
- Humans
- Lipid Peroxidation
- Male
- Middle Aged
- Oxidative Stress
- Oxygen Consumption
- Signal Transduction
- Superoxide Dismutase
- Young Adult
Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar-Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively. F1 control and restricted females were mated with normal males, resulting in F2 control and restricted offspring, respectively. F1 restricted male offspring were significantly lighter at birth (P < 0.05), but there were no differences in birthweight of F2 offspring. Left ventricular weights and volumes were significantly increased (P < 0.05) in F1 and F2 restricted offspring at day 35. Left ventricular cardiomyocyte number was not different in F1 and F2 restricted offspring. At 6 months-of-age, F1 and F2 restricted offspring had elevated blood pressure (8-15 mmHg, P < 0.05). Our findings demonstrate the emergence of left ventricular hypertrophy and hypertension, with no change in cardiomyocyte number, in F1 restricted male offspring, and this was transmitted to the F2 offspring. The findings support transgenerational programming effects.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Birth Weight
- Disease Models, Animal
- Female
- Fetal Growth Retardation
- Heart Ventricles
- Hypertension
- Hypertrophy, Left Ventricular
- Male
- Organ Size
- Placental Circulation
- Placental Insufficiency
- Pregnancy
- Prenatal Exposure Delayed Effects
- Rats, Inbred WKY
- Sex Characteristics
Keywords
- blood pressure
- cardiomyocyte number
- growth restriction
- left ventricular hypertrophy
- transgenerational transmission
We previously reported that insulin-like growth factor 1 (IGF1) was involved in coregulating female sexual maturation and longevity. To understand the underlying genetic mechanisms, based on the strain survey assays of development and aging traits, we crossed two mouse strains, KK/HIJ and PL/J, and produced 307 female F2 mice. We observed the age of vaginal patency (AVP) and the life span of these females. We also measured circulating IGF1 level at 7, 16, 24, 52, and 76 weeks. IGF1 level at 7 weeks significantly correlated with AVP. IGF1 levels at ages of 52 and 76 weeks negatively correlated with longevity (p ≤ .05). A gene mapping study found 22, 4 ,and 3 quantitative trait loci for IGF1, AVP, and life span, respectively. Importantly, the colocalization of IGF1, AVP, and life span quantitative trait loci in the distal region of chromosome 2 suggests this locus carries gene(s) that could regulate IGF1, AVP, and life span. In this region, proprotein convertase subtilisin/kexin type 2 has been found to be associated with female sexual maturation in a human genome-wide association study. We verified the roles of proprotein convertase subtilisin/kexin type 2 in regulating IGF1 and AVP by showing that depletion of proprotein convertase subtilisin/kexin type 2 significantly reduced IGF1 and delayed AVP in mice, suggesting that it also might be involved in the regulation of aging.
MeSH Terms
- Animals
- Chromosome Mapping
- Female
- Insulin-Like Growth Factor I
- Lod Score
- Longevity
- Mice
- Mice, Inbred Strains
- Proprotein Convertase 2
- Quantitative Trait Loci
- Sexual Maturation
Keywords
- Female sexual maturation
- Genetics
- Life span
- Mouse
- Pcsk2.
The Healthy Brain Initiative 2013-2018 seeks to optimize brain health as we age. Free radical injury is an important effector of molecular and cellular stress in the aging brain that derives from multiple sources. To identify potentially modifiable risk factors associated with increased markers of brain oxidative stress. This cross-sectional, academic multicenter study consisted of 320 research volunteers (172 women) aged 21 to 100 years who were medically healthy and cognitively normal. Free radical injury to the brain was assessed using cerebrospinal fluid (CSF) F2-isoprostane (F2-IsoP) concentrations correlated with age, sex, race, cigarette smoking, body mass index, inheritance of the ε4 allele of the apolipoprotein E gene (APOE), and CSF biomarkers of Alzheimer disease. The concentration of CSF F2-IsoP increased with age by approximately 3 pg/mL (approximately 10%) from age 45 to 71 years in medically healthy, cognitively normal adults (P < .001). The CSF F2-IsoP concentration increased by approximately more than 10% for every 5-U increase in body mass index (P < .001). Current smoking had an approximately 3-fold greater effect on CSF F2-IsoPs compared with age (P < .001). Women had greater mean CSF F2-IsoP concentrations than men at all ages after adjusting for other factors (P = .02). Neither the concentration of CSF Alzheimer disease biomarkers nor inheritance of the APOE ε4 allele was associated with the CSF F2-IsoP concentration in this group of medically healthy, cognitively normal adults (P > .05). The association between CSF F2-IsoP concentrations and race was not significant after controlling for the effect of current smoking status (P = .45). Our results are consistent with an age-related increase in free radical injury in the human brain and uniquely suggest that this form of injury may be greater in women than in men. Our results also highlighted 2 lifestyle modifications (ie, body mass index and smoking) that would have an even greater effect on suppressing free radical injury to the brain than would suppressing the processes of aging. These results inform efforts to achieve success in the Healthy Brain Initiative 2013-2018.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Apolipoprotein E4
- Biomarkers
- Body Mass Index
- Brain
- Cross-Sectional Studies
- F2-Isoprostanes
- Female
- Free Radicals
- Humans
- Life Style
- Male
- Middle Aged
- Sex Factors
- Smoking
- Young Adult
Previous evidences support that increased oxidative stress (OxS) may play an important role in metabolic syndrome (MetS) and both are closely linked to vascular dysfunction. This study determined whether there is a relationship between endothelial function and relative telomere length (RTL) in MetS subjects. In this cross-sectional study from the LIPGENE cohort, a total of 88 subjects (36 men and 52 women) were divided into four groups by quartiles of telomere length. We measured ischemic reactive hyperemia (IRH), total nitrite (NO) and protein carbonyl (PC) plasma levels, F2-isoprostanes urinary levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. IRH and NO plasma levels were higher in subjects with longer RTL (quartiles 3 and 4), while PC plasma levels, F2-isoprostanes urinary levels, and GPx and SOD plasma activities were lower in quartile 4 subjects (longest RTL). Additionally, MetS subjects with longer RTL had greater homeostatic model assessment-β level and lower triglycerides plasma levels. Our results suggest that endothelial dysfunction, associated with high levels of OxS, could be entailed in an increment of telomere attrition. Thus, further support of the molecular and cellular mechanisms involved in vascular dysfunction may contribute to the development of strategies to decelerate vascular aging or prevent cardiovascular disease.
MeSH Terms
- Aging
- Cardiovascular Diseases
- Cross-Sectional Studies
- DNA
- Endothelium, Vascular
- Europe
- Female
- Follow-Up Studies
- Humans
- Incidence
- Male
- Metabolic Syndrome
- Middle Aged
- Oxidative Stress
- Polymerase Chain Reaction
- Telomere
- Vasodilation
A novel rice mutant, lesion mimic and early senescence 1 (lmes1), was induced from the rice 93-11 cultivar in a γ-ray field. This mutant exhibited spontaneous disease-like lesions in the absence of pathogen attack at the beginning of the tillering stage. Moreover, at the booting stage, lmes1 mutants exhibited a significantly increased MDA but decreased chlorophyll content, soluble protein content and photosynthetic rate in the leaves, which are indicative of an early senescence phenotype. The lmes1 mutant was significantly more resistant than 93-11 against rice bacterial blight infection, which was consistent with a marked increase in the expression of three resistance-related genes. Here, we employed a map-based cloning approach to finely map the lmes1 gene. In an initial mapping with 94 F2 individuals derived from a cross between the lmes1 mutant and Nipponbare, the lmes1 gene was located in a 10.6-cM region on the telomere of the long arm of chromosome 7 using simple sequence repeat (SSR) markers. To finely map lmes1, we derived two F2 populations with 940 individuals from two crosses between the lmes1 mutant and two japonica rice varieties, Nipponbare and 02428. Finally, the lmes1 gene was mapped to an 88-kb region between two newly developed inDel markers, Zl-3 and Zl-22, which harbored 15 ORFs.
MeSH Terms
- Oryza
- Photosynthesis
- Plant Proteins
Keywords
- Early senescence
- Fine mapping
- Lesion mimic mutant
- Oryza sativa L
- lmes1
Obesity and type 2 diabetes have a heritable component that is not attributable to genetic factors. Instead, epigenetic mechanisms may play a role. We have developed a mouse model of intrauterine growth restriction (IUGR) by in utero malnutrition. IUGR mice developed obesity and glucose intolerance with aging. Strikingly, offspring of IUGR male mice also developed glucose intolerance. Here, we show that in utero malnutrition of F1 males influenced the expression of lipogenic genes in livers of F2 mice, partly due to altered expression of Lxra. In turn, Lxra expression is attributed to altered DNA methylation of its 5' UTR region. We found the same epigenetic signature in the sperm of their progenitors, F1 males. Our data indicate that in utero malnutrition results in epigenetic modifications in germ cells (F1) that are subsequently transmitted and maintained in somatic cells of the F2, thereby influencing health and disease risk of the offspring.
MeSH Terms
- Aging
- Animals
- Cells, Cultured
- DNA Methylation
- Epigenesis, Genetic
- Female
- Fetal Growth Retardation
- Glucose Intolerance
- Lipid Metabolism
- Lipogenesis
- Liver
- Liver X Receptors
- Male
- Malnutrition
- Mice
- Mice, Inbred ICR
- Obesity
- Orphan Nuclear Receptors
- Pregnancy
- Spermatozoa
- Sterol Regulatory Element Binding Protein 1
Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury. To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait. Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years. To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F2-isoprostanes (measures of free radical injury). Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F2-isoprostane concentration was significantly associated with poorer executive function (adjusted R2 ≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal R2 ≤0.31). Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Amyloid beta-Peptides
- Biomarkers
- Cognition Disorders
- Cross-Sectional Studies
- Female
- Humans
- Male
- Middle Aged
- Neuropsychological Tests
- tau Proteins
The sterile insect technique (SIT) is an alternative, environmentally friendly method for controlling insect pests. In the Lepidoptera, a low dose of gamma irradiation causes inherited sterility (SIT-IS), leading to full sterility in females but only partial sterility in males, which successfully compete with wild males for mates. This study examined the effect of a low radiation dose (150 Gy) on the fitness parameters of male and female Lobesia botrana, a polyphagous and major pest of vineyards found in the Middle East, Europe and the Americas. Irradiation of the pupae did not affect their emergence rate, flight ability out of a cylinder, male response to sex pheromone in a field cage or male or female mating success. A major effect of irradiation was observed in the significantly reduced number of irradiated females' offspring reaching pupation, and as a consequence a limited number of F2 offspring. The effect of irradiation on male partial sterility (also called inherited sterility) was reflected in the male-biased sex ratio of F1 offspring of irradiated males, the reduced number of F1 offspring and the very low number of F2 descendants. This study demonstrates the feasibility of controlling L. botrana using SIT-IS. Adding this method to the arsenal of environmentally friendly tools to control this pest may assist in further reducing the use of insecticides on edible crops.
MeSH Terms
- Animals
- Female
- Flight, Animal
- Longevity
- Male
- Metamorphosis, Biological
- Moths
- Oviposition
- Pest Control, Biological
- Sexual Behavior, Animal
Keywords
- Lepidoptera
- SIT-IS
- control
- fecundity
- fitness
- irradiation
- sterile insect technique
We theorized that progressive bladder dysfunction due to clinical diagnoses such as outlet obstruction occurs as a result of cyclical oxidative stress events. We hypothesized that measurement of F2-isoprostane, a marker of lipid peroxidation, could serve as a biomarker of oxidative stress in the murine bladder. At age 5 to 6 weeks oophorectomized female mice were subjected to 1 of 2 bladder injury models, that is partial bladder outlet obstruction or acute bladder distension. The time points studied after injury included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute bladder distension. In a separate group short-term repetitive acute bladder distension was performed every other day for 14 days. Bladder samples were analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean tissue F2-isoprostane levels were compared. F2-isoprostane increased significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39 and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant increase in F2-isoprostane immediately after distension compared to controls (1.6 vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder distension F2-isoprostane did not change. Measurement of tissue F2-isoprostane in the bladder reflects the progression of oxidative stress, primarily in chronic injury models such as partial bladder outlet obstruction. The usefulness of F2-isoprostane measurements in shorter term injury models requires further study.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Disease Models, Animal
- Disease Progression
- F2-Isoprostanes
- Female
- Mice
- Oxidative Stress
- Reactive Oxygen Species
- Urinary Bladder Neck Obstruction
Keywords
- F(2)-isoprostanes
- mice
- oxidative stress
- urinary bladder
- urinary bladder neck obstruction
In Moscow region long-livers we have studied distribution of LPL, CETP, APOE, F2, F5, F7, F13, FGB, ITGA2, ITGB3, PAI-1, MTHFR, MTRR, HLA-DRB1, HLA-DQA1, HLA-DQB1 genes polymorphisms, associated with predisposition to age pathology. Long-livers are characterized by favorable course of cardiovascular diseases accompanied by certain genetic factors. We have established that genotype H-H- of LPL, allele epsilon2 of APOE, genotype CC of MTHFR (677C > T), genotype TC of ITGB3, genotype GA of FGB, HLA-DRB1*11 positively correlate with longevity.
MeSH Terms
- Aged
- Aged, 80 and over
- Alleles
- Cardiovascular Diseases
- Female
- Gene Frequency
- Genetic Markers
- Genetic Predisposition to Disease
- Genotype
- Humans
- Longevity
- Male
- Moscow
- Polymorphism, Genetic
- Prevalence
- Urban Population
Chagas disease develops upon infection with the protozoan parasite Trypanosoma cruzi and undergoes an acute phase characterized by massive parasite replication and the presence of parasites in the blood. This condition is known as acute phase parasitemia. This initial stage may result in a cure, in the development of the chronic stages of the disease or in the death of the infected host. Despite intensive investigation related to the characterization of the acute and chronic phases of the disease, the cause-effect relationship of acute phase parasitemia to the outcome of the disease is still poorly understood. In this study, we artificially generated a heterogeneously controlled mouse population by intercrossing F1 mice obtained from a parental breeding of highly susceptible A/J with highly resistant C57BL/6 mouse strains. This F2 population was infected and used to assess the correlation of acute phase parasitemia with the longevity of the animals. We used nonparametric statistical analyses and found a significant association between parasitemia and mortality. If males and females were evaluated separately, we found that the former were more susceptible to death, although parasitemia was similar in males and females. In females, we found a strong negative correlation between parasitemia and longevity. In males, however, additional factors independent of parasitemia may favor mouse mortality during the development of the disease. The correlations of acute phase parasitemia with mortality reported in this study may facilitate an appropriate prognostic approach to the disease in humans. Moreover, these results illustrate the complexity of the mammalian genetic traits that regulate host resistance during Chagas disease.
MeSH Terms
- Acute-Phase Reaction
- Animals
- Chagas Disease
- Crosses, Genetic
- Female
- Longevity
- Male
- Mice, Inbred C57BL
- Parasitemia
- Sex Characteristics
- Survival Analysis
- Trypanosoma cruzi
Even within a single genus, such as Drosophila, cases of lineage-specific adaptive evolution have been found. Therefore, the molecular basis of phenotypic variation must be addressed in more than one species group, in order to infer general patterns. In this work, we used D. americana, a species distantly-related to D. melanogaster, to perform an F2 association study for developmental time (DT), chill-coma recovery time (CRT), abdominal size (AS) and lifespan (LS) involving the two strains (H5 and W11) whose genomes have been previously sequenced. Significant associations were found between the 43 large indel markers developed here and DT, AS and LS but not with CRT. Significant correlations are also found between DT and LS, and between AS and LS, that might be explained by variation at genes belonging to the insulin and ecdysone signaling pathways. Since, in this F2 association study a single marker, located close to the Ecdysone receptor (EcR) gene, explained as much as 32.6% of the total variation in DT, we performed a second F2 association study, to determine whether large differences in DT are always due to variation in this genome region. No overlapping signal was observed between the two F2 association studies. Overall, these results illustrate that, in D. americana, pleiotropic genes involved in the highly-conserved insulin and ecdysone signaling pathways are likely responsible for variation observed in ecologically relevant phenotypic traits, although other genes are also involved.
MeSH Terms
- Abdomen
- Animals
- Crosses, Genetic
- Drosophila
- Ecdysone
- Female
- Genes, Insect
- Genetic Association Studies
- Genetic Variation
- Insulin
- Longevity
- Male
- Organ Size
- Phenotype
- Quantitative Trait, Heritable
- Signal Transduction
- Time Factors
Oxidative stress caused by reactive oxygen species is proposed to cause age related muscle wasting (sarcopenia). Reversible oxidation of protein thiols by reactive oxygen species can affect protein function, so we evaluated whether muscle wasting in normal aging was associated with a pervasive increase in reversible oxidation of protein thiols or with an increase in irreversible oxidative damage to macromolecules. In gastrocnemius muscles of C57BL/6J female mice aged 3, 15, 24, 27, and 29 months there was no age related increase in protein thiol oxidation. In contrast, there was a significant correlation (R (2) = 0.698) between increasing protein carbonylation, a measure of irreversible oxidative damage to proteins, and loss of mass of gastrocnemius muscles in aging female mice. In addition, there was an age-related increase in lipofuscin content, an aggregate of oxidised proteins and lipids, in quadriceps limb muscles in aging female mice. However, there was no evidence of an age-related increase in malondialdehyde or F2-isoprostanes levels, which are measures of oxidative damage to lipids, in gastrocnemius muscles. In summary, this study does not support the hypothesis that a pervasive increase in protein thiol oxidation is a contributing factor to sarcopenia. Instead, the data are consistent with an aging theory which proposes that molecular damage to macromolecules leads to the structural and functional disorders associated with aging.
MeSH Terms
- Aging
- Animals
- Female
- Lipofuscin
- Malondialdehyde
- Mice
- Mice, Inbred C57BL
- Models, Animal
- Muscle, Skeletal
- Oxidation-Reduction
- Reactive Oxygen Species
- Sarcopenia
- Sulfhydryl Compounds
The question of whether or not perennial plants senesce at the organism level remains unresolved. The aim of this study was to unravel whether or not plant age can influence the production and composition of seeds. Flower and seed production was examined in 3-, 8-, and 13-year-old Cistus albidus plants growing in experimental plots corresponding to the F2, F1, and F0 generations of the same population. Furthermore, the phytohormone, fatty acid, and vitamin E content of the seeds was evaluated, and their viability was examined. Whether or not age-related differences in seed quality were observed in a natural population in the Montserrat Mountains (NE Spain) was also tested. The results indicate that under controlled conditions, the oldest plants not only produced fewer flowers, but also had higher rates of embryo abortion in mature seeds. However, germination capacity was not negatively affected by plant ageing. Seeds of the oldest plants contained significantly higher salicylic acid, jasmonic acid, and vitamin E levels compared with those from younger plants. Despite vigour (in terms of plant growth) being severely reduced due to harsh environmental conditions in the natural population, the oldest individuals produced seeds with no decline in viability. Seed biomass was instead positively correlated with seed viability. In conclusion, increased plant size may explain the loss of seed viability in the experimental field, but older smaller individuals in natural populations can escape senescence in terms of seed viability loss.
MeSH Terms
- Abscisic Acid
- Biomass
- Cistus
- Cyclopentanes
- Fatty Acids
- Flowers
- Fruit
- Germination
- Indoleacetic Acids
- Oxylipins
- Phenotype
- Plant Growth Regulators
- Plant Leaves
- Salicylic Acid
- Seeds
- Spain
- Time Factors
- Vitamin E
Keywords
- Ageing
- Cistus albidus L.
- perennials
- seed composition
- seed production
- senescence
- vitamin E.
Since a reduction of the insulin/IGF-1 signaling cascade extends life span in many species and IGF-1 signaling might partly mediate the effects of caloric restriction (CR), an experimental intervention for increasing longevity, the purpose of the present study was to use quantitative trait loci (QTL) analysis, an unbiased genetic approach, to identify particular regions of the genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C rats; the latter being an inbred strain of Wistar origin, considered as a model of healthy aging since it resists to age (and diet)-induced obesity. F1 hybrids were obtained by crossbreeding LOU/C with F344 rats, and then F1 were bred inter se to obtain the F2 population, of which 93 males and 94 females were studied. Total plasma IGF-1 levels were determined by radioimmunoassay. A genome scan of the F2 population was made with 100 microsatellite markers) selected for their polymorphism between LOU/C and F344 strains (and by covering evenly the whole genome. By simple interval mapping sex-dependent QTLs were found on chromosome 17 in males and on chromosome 18 in females. By multiple interval mapping, additional QTLs were found on chromosomes 1, 4, 5, 6, 12, 15 and 19 in males and on chromosomes 3, 5, 6, 12 and 17 in females. Only the markers D1Rat196 and D12Mgh5 were found in both males and females. The majority of QTLs corresponded to metabolic syndrome (cardiac function: n = 45 (30%), obesity/diabetes: n = 22 (15%), inflammation: n = 19 (13%) and only a limited number to body weight: n = 13 (9%), proliferation (n = 10 (7%) or ossification: n = 7 (5%). Ninety-six candidate genes were located on the different QTLs. A significant proportion of these genes are connected to IGF-1 production and receptor pathways (n = 18) or metabolic syndrome (n = 11). Subsequent studies are necessary to determine whether the genetic networks underscored are also involved in age-associated obesity, diabetes and inflammation as well as cardiovascular impairments.
MeSH Terms
- Aging
- Animals
- Crosses, Genetic
- Female
- Insulin-Like Growth Factor I
- Lod Score
- Male
- Metabolic Networks and Pathways
- Phenotype
- Quantitative Trait Loci
- Radioimmunoassay
- Rats
- Rats, Inbred F344
- Rats, Wistar
Keywords
- Ageing
- Energy metabolism
- Inflammation
- Metabolic syndrome
"See-through" strains of medaka are unique tools for experiments: their skin is transparent, and their internal organs can be externally monitored throughout life. However, see-through fish are less vital than normally pigmented wild-type fish, which allows only skilled researchers to make the most of their advantages. Expecting that hybrid vigor (heterosis) would increase the vitality, we outcrossed two see-through strains (SK(2) and STIII) with a genetically distant wild-type strain (HNI). Fish with the see-through phenotypes were successfully restored in the F2 generation and maintained as closed colonies. We verified that genomes of these hybrid see-through strains actually consisted of approximately 50% HNI and approximately 50% SK(2) or STIII alleles, but we could not obtain evidence supporting improved survival of larvae or fecundity of adults, at least under our breeding conditions. We also found that four of the five see-through mutations (b(g8), i-3, gu, and il-1 but not lf) additively decrease viability. Given that heterosis could not overwhelm the viability-reducing effects of the see-through mutations, easy-to-breed see-through strains will only be established by other methods such as conditional gene targeting or screening of new body-color mutations that do not reduce viability.
MeSH Terms
- Alleles
- Animals
- Breeding
- Crossing Over, Genetic
- Genome
- Genotype
- Hybrid Vigor
- Longevity
- Membrane Transport Proteins
- Mutation
- Oryzias
- Phenotype
- Skin Pigmentation
Keywords
- guanineless
- iridophoreless-1
- leucophore free
- medaka
- oculocutaneous albinism type 2 (oca2)
- solute carrier family 45 member 2 (slc45a2)
This study demonstrates inducible transgenic expression in the exceptionally short-lived turquoise killifish Nothobranchius furzeri, which is a useful vertebrate model for ageing research. Transgenic N. furzeri bearing a green fluorescent protein (Gfp) containing construct under the control of a heat shock protein 70 promoter were generated, heat shock-induced and reversible Gfp expression was demonstrated and germline transmission of the transgene to the F1 and F2 generations was achieved. The availability of this inducible transgenic expression system will make the study of ageing-related antagonistically pleiotropic genes possible using this unique vertebrate model organism.
MeSH Terms
- Animals
- Animals, Genetically Modified
- Gene Expression Regulation
- Killifishes
- Longevity
There is still controversy whether adverse effects by genotoxic anthropogenic pollutants are linked to the decline of fish populations. Further investigations into the relationship between genotoxic stress and detrimental effects on development and reproduction in fish are required. For this end, zebrafish (F0 generation) were exposed in vivo to the alkylating model genotoxin methyl methanesulfonate (MMS) from fertilization to the age of 1 year. F0 fish were mated over 6 months to check for reproductive capacities. F1 fish grew up without exposure in order to allow for regeneration. Mortality of F0 fish depended on MMS concentrations. In MMS-exposed F0 fish, times of first spawning were delayed and fertility was reduced. Using the alkaline comet assay and the micronucleus test, significant genotoxic effects were found in the livers, gills and gonads of either sex in the F0 generation. No detrimental effects on growth were found. In F1 fish with parental exposure, teratogenic effects were increased, and larval survival was reduced. However, fertility capacities of the non-exposed F1 generation had recovered. Development and survival rates further recovered in the F2 generation. Anthropogenic genotoxicants may thus play a considerable role in the decline of wild fish populations.
MeSH Terms
- Abnormalities, Drug-Induced
- Animals
- Comet Assay
- DNA
- DNA Damage
- Female
- Life Cycle Stages
- Longevity
- Male
- Methyl Methanesulfonate
- Micronuclei, Chromosome-Defective
- Micronucleus Tests
- Mutagens
- Recovery of Function
- Reproduction
- Water Pollutants
- Zebrafish
Understanding the molecular basis of within and between species phenotypic variation is one of the main goals of Biology. In Drosophila, most of the work regarding this issue has been performed in D. melanogaster, but other distantly related species must also be studied to verify the generality of the findings obtained for this species. Here, we make the case for D. americana, a species of the virilis group of Drosophila that has been diverging from the model species, D. melanogaster, for approximately 40 Myr. To determine the suitability of this species for such studies, polymorphism and recombination estimates are presented for D. americana based on the largest nucleotide sequence polymorphism data set so far analyzed (more than 100 data sets) for this species. The polymorphism estimates are also compared with those obtained from the comparison of the genome assembly of two D. americana strains (H5 and W11) here reported. As an example of the general utility of these resources, we perform a preliminary study on the molecular basis of lifespan differences in D. americana. First, we show that there are lifespan differences between D. americana populations from different regions of the distribution range. Then, we perform five F2 association experiments using markers for 21 candidate genes previously identified in D. melanogaster. Significant associations are found between polymorphism at two genes (hep and Lim3) and lifespan. For the F2 association study involving the two sequenced strains (H5 and W11), we identify amino acid differences at Lim3 and Hep that could be responsible for the observed changes in lifespan. For both genes, no large gene expression differences were observed between the two strains.
MeSH Terms
- Amino Acid Sequence
- Animals
- Biological Evolution
- Drosophila
- Drosophila Proteins
- Drosophila melanogaster
- Genome, Insect
- Life Expectancy
- Models, Genetic
- Molecular Sequence Data
- Phenotype
- Sequence Alignment
Comparisons of quantitative trait loci (QTL) for growth and parameters of growth curves assist in understanding the genetics and ultimately the physiology of growth. Records of body weight at 3, 6, 12, 24, 48 and 72 weeks of age and growth rate between successive age intervals of about 500 F2 female chickens of the Roslin broiler-layer cross were available for analysis. These data were analysed to detect and compare QTL for body weight, growth rate and parameters of the Gompertz growth function. Over 50 QTL were identified for body weight at specific ages and most were also detected in the nearest preceding and/or subsequent growth stage. The sum of the significant and suggestive additive effects for bodyweight at specific ages accounted for 23-43% of the phenotypic variation. A single QTL for body weight on chromosome 4 at 48 weeks of age had the largest additive effect (550.4 ± 68.0 g, 11.5% of the phenotypic variation) and a QTL at a similar position accounted 14.5% of the phenotypic variation at 12 weeks of age. Age specific QTL for growth rate were detected suggesting that there are specific genes that affect developmental processes during the different stages of growth. Relatively few QTL influencing Gompertz growth curve parameters were detected and overlapped with loci affecting growth rate. Dominance effects were generally not significant but from 12 weeks of age they exceeded the additive effect in a few cases. No evidence for epistatic QTL pairs was found. The results confirm the location for body weight and body weight gain during growth that were identified in previous studies and were consistent with QTL for the parameters of the Gompertz growth function. Chromosome 4 explained a relatively large proportion of the observed growth variation across the different ages, and also harboured most of the detected QTL for Gompertz parameters, confirming its importance in controlling growth. Very few QTL were detected for body weight or gain at 48 and 72 weeks of age, probably reflecting the effect of differences in reproduction and random environmental effects.
MeSH Terms
- Aging
- Animals
- Body Weight
- Chickens
- Female
- Male
- Models, Biological
- Quantitative Trait Loci
Vitamin D less-calcemic analog JKF 1624 F2-2 (JKF) and PTH 1-34 stimulate in human female cultured osteoblasts (Ob) DNA synthesis (DNA), creatine kinase specific activity (CK), 1α, 25 vitamin D hydroxylase mRNA (1OHase) expression and 1,25(OH)2D3 (1,25) production, estrogen receptors (ER) mRNA expression and intracellular and membranal estrogen binding. In the present study, cultured Ob from different ages were subjected to hormonal stimulations and analyzed for different parameters. We found: 1) ERα expression is higher and ERβ expression is lower in pre-meno - pausal Ob (prOb), with similar intracellular and membranal binding. 2) JKF and PTH up-regulated ERα and JKF downregulated ERβ in both Ob, while PTH stimulated it in post- (poOb) and inhibited it in prOb. 3) There is higher expression of 1OHase mRNA in prOb, but 1,25 production is similar. Both parameters were hormonally stimulated to higher extent in prOb. 4) Ob express 12 and 15 lipoxygenase (LO) mRNA and produce 12- and 15-hydroxyeicosatetraenoic acid (H). 12LO expression is higher and 15LO is lower in prOb, while 12H is higher in prOb and 15H is similar in both. JKF inhibited 12LO expression in prOb and stimulated in poOb, whereas PTH stimulated it to higher extent in prOb. JKF stimulated and PTH inhibited 15LO expression in both; 12 and 15H were stimulated by both hormones in both Ob. 5. PTH and JKF stimulated DNA and CK in both Ob. In conclusion Ob demonstrate some age-dependent response to calciotrophic hormones, but the mechanism and beneficial outcome for human is unclear.
MeSH Terms
- Age Factors
- Aging
- Cells, Cultured
- Female
- Humans
- Osteoblasts
- Parathyroid Hormone
- Postmenopause
- Premenopause
- Receptors, Estrogen
- Vitamin D
Dietary restriction is a powerful aging intervention that extends the life span of diverse biological species ranging from yeast to invertebrates to mammals, and it has been argued that the antiaging action of dietary restriction occurs through reduced oxidative stress/damage. Using Sod1(-/-) mice, which have previously been shown to have increased levels of oxidative stress associated with a shorter life span and a high incidence of neoplasia, we were able to test directly the ability of dietary restriction to reverse an aging phenotype due to increased oxidative stress/damage. We found that dietary restriction increased the life span of Sod1(-/-) mice 30%, returning it to that of wild-type, control mice fed ad libitum. Oxidative damage in Sod1(-/-) mice was markedly reduced by dietary restriction, as indicated by a reduction in liver and brain F2-isoprostanes, a marker of lipid peroxidation. Analysis of end of life pathology showed that dietary restriction significantly reduced the overall incidence of pathological lesions in the Sod1(-/-) mice fed the dietary-restricted diet compared to Sod1(-/-) mice fed ad libitum, including the incidence of lymphoma (27 vs 5%) and overall liver pathology. In addition to reduced incidence of overall and liver-specific pathology, the burden and severity of both neoplastic and nonneoplastic lesions was also significantly reduced in the Sod1(-/-) mice fed the dietary-restricted diet. These data demonstrate that dietary restriction can significantly attenuate the accelerated aging phenotype observed in Sod1(-/-) mice that arises from increased oxidative stress/damage.
MeSH Terms
- Aging
- Animals
- Brain
- Diet
- F2-Isoprostanes
- Humans
- Lipid Peroxidation
- Liver
- Male
- Mice
- Oxidation-Reduction
- Oxidative Stress
- Superoxide Dismutase
- Superoxide Dismutase-1
Maternal nicotine exposure during gestation and lactation adversely affects lung development in the offspring. It has been suggested that the "program" that control long-term maintenance of the structural integrity of the lung may be compromised. The aim of the study was to establish whether the effect of grand-maternal nicotine exposure during gestation and lactation can be transferred to the F2 generation. After mating, rats were randomly divided into two groups (F0). One group received nicotine (1 mg/kg body weight/day). The controls receive saline. Body weight (BW), lung volume (Lv), linear intercept (Lm), alveolar wall thickness (Tsept), senescent and proliferating cell numbers were used to evaluate changes in the lung structure of the offspring (F1). The F1 generation was divided into four groups, namely, (1) control (F1 males mated with F1 females, (2) NmCf (F1 nicotine exposed male mated with F1 control female), (3) NfCm (F1 nicotine exposed female mated with F1 control male), and (4) NmNf (F1 male exposed to nicotine mated with F1 female also exposed to nicotine). The F1 nicotine exposed males and females were exposed to nicotine via the placenta and mother's milk (F0 generation) only. The F2 progeny was never exposed to nicotine. Grand-maternal nicotine (F0) resulted in parenchymal deterioration and emphysema in the F2 progeny due to increased numbers of premature senescent cells together with a slower cell proliferation. The transfer of premature aging characteristics from the F1 progeny to the F2 progeny is via the male and female germ cell line. Grand-maternal nicotine exposure induces structural changes in the lungs of the F2 generation that resembled premature aging.
MeSH Terms
- Animals
- Emphysema
- Female
- Lactation
- Lung
- Male
- Maternal Exposure
- Nicotine
- Pregnancy
- Rats
Keywords
- F2 generation
- cell proliferation
- cell senescence
- emphysema
- grand maternal nicotine exposure
{{medline-entry |title=Influence of Orientia tsutsugamushi infection on the developmental biology of Leptotrombidium imphalum and Leptotrombidium chiangraiensis (Acari: Trombiculidae). |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23270154 |abstract=Leptotrombidium chiangraiensis Tanskul