C6
Complement component C6 precursor
Publications[править]
Neuromuscular dysfunction is common in old age. Damaged cytoplasmic structures aggregate with aging, especially in post-mitotic cells like motor neurons. Autophagy is a ubiquitous cell process that aids in the clearance of damaged aggregates. Accordingly, we hypothesized that autophagy is impaired in old age, contributing to neuromuscular dysfunction via an effect in motor neurons. Autophagy flux may be impaired as a result of deficits in the initiation, elongation or degradation phases. Changes in the expression levels of core proteins necessary for each of the autophagy phases were evaluated by Western blotting in the cervical spinal cord (segments C2-C6 corresponding to the phrenic motor pool) of adult male and female mice at 6-, 18-, and 24-months of age (reflecting 100%, 90% and 75% survival, respectively). There was no evidence of an effect of age on the expression of the autophagy markers Beclin-1 (Becn-1; initiation), ATG7 and ATG5/12 complex (elongation) or LC3 (elongation/degradation). Reduced p62 expression (a marker of degradation) was evident in the cervical spinal cord of adult mice at 18-months compared to 24-months. Accordingly, expression of LC3 and p62 in motor neurons was analyzed using immunofluorescence and confocal microscopy in separate animals. LC3 and p62 immunoreactivity was evident in the gray matter with minimal expression in the white matter across all age groups. A mixed linear model with animal as a random effect was used to compare relative LC3 and p62 expression in motor neurons to gray matter across age groups. Expression of both LC3 and p62 was higher in choline acetyl transferase (ChAT)-positive motor neurons (~2-3 fold vs. gray matter). Across age groups, there were differences in the relative expression of LC3 (F = 7.59, p < 0.01) and p62 (F = 8.00, p < 0.01) in cervical motor neurons. LC3 expression in motor neurons increased ~20% by 24-months of age in both male and female mice. p62 expression in motor neurons increased ~70% by 18-months compared to 6-months with no further changes by 24-months of age in male mice. p62 expression did not change across age groups in female mice, and was ~20% higher than in males. Our findings highlight important changes in autophagy pathways that likely contribute to the development of aging-related neuromuscular dysfunction in mice. At 18-months of age, increased autophagosome clearance (reduced p62 expression) appears to be a global effect not restricted to motor neurons. By 24-months of age, increased expression of LC3 and p62 indicates impaired autophagy with autophagosome accumulation in cervical motor neurons.
Keywords
- Aging
- Autophagy
- Motor neuron
- Neuromuscular dysfunction
- Spinal cord
Aroma is a crucial attribute for wine quality, particularly in white wines. Traditionally, the consumption of young white wines is recommended over the year following grape harvest due to potential aroma losses that would worsen wine quality. This study aimed to investigate the evolution of volatile compounds, odor activity value-based aroma notes, and sensory perception in Treixadura ([i]Vitis vinifera[/i] L.) dry white wines during a 24-month bottle-aging period. Volatile composition was determined by gas chromatography, and wine sensory evaluation was performed by experts. Wine samples had similar volatile compositions at the time of bottling. The volatile contents of the wines were respectively 322.9, 302.7, 323.0, and 280.9 mg L after 6, 12, 18, and 24 months of bottle storage. Most of the volatiles tended to maintain constant concentrations, or with slight increases in all families of volatiles except for acetates and carbonyl compounds, until two years after harvest (18 months of bottle storage) and, then, concentrations reduced sharply. After 24 months of storage in the bottle, the concentrations of terpenes, C6 compounds, higher alcohols, ethyl esters, fatty acids, acetates, carbonyl compounds, and volatile phenols were reduced by 32%, 47%, 11%, 39%, 50%, 74%, 41%, and 54%, respectively. The 18-month bottle-aged wines showed the highest concentrations of volatiles, as well as the best performance in the sensory evaluation, suggesting that a good balance of the aroma attributes was achieved on this date. In conclusion, the current study suggests that Treixadura wines expressed their maximum aroma potential two years after grape harvest.
Keywords
- bottle aging
- flavor profile
- sensory evaluation
- volatile composition
- white wine
Treatment of glioblastoma using radiotherapy and chemotherapy has various outcomes, key among them being cellular senescence. However, the molecular mechanisms of this process remain unclear. In the present study, we tested the ability of D-galactose (D-gal), a reducing sugar, to induce senescence in glioblastoma cells. Following pretreatment with D-gal, glioblastoma cell lines (C6 and U87MG) showed typical characteristics of senescence. These included the reduced cell proliferation, hypertrophic morphology, increased senescence-associated β-galactosidase activity, downregulation of Lamin B1, and upregulation of several senescence-associated genes such as p16, p53, and NF-κB. Furthermore, our results showed that D-gal was more suitable than etoposide (a DNA-damage drug) in inducing senescence of glioblastoma cells. Mechanistically, D-gal inactivated the YAP-CDK6 signaling pathway, while overexpression of YAP or CDK6 could restore D-gal-induced senescence of C6 cells. Finally, metformin, an anti-aging agent, activated the YAP-CDK6 pathway and suppressed D-gal-induced senescence of C6 cells. Taken together, these findings established a new model for analyzing senescence in glioblastoma cells, which occurred through the YAP-CDK6 pathway. This is expected to provide a basis for development of novel therapies for the treatment of glioblastoma.
Keywords
- CDK6
- D-galatose
- YAP
- cellular senescence
- glioblastoma
Age-related changes in methylation are involved in the occurrence and development of tumors, autoimmune disease, and nervous system disorders, including Alzheimer's disease (AD), in elderly individuals; hence, modulation of these methylation changes may be an effective strategy to delay the progression of AD pathology. In this study, the AD model rats were used to screen the main active extracts from the mushroom, [i]Ganoderma lucidum[/i], for anti-aging properties, and their effects on DNA methylation were evaluated. The results of evaluation of rats treated with 100 mg/kg/day of D-galactose to induce accelerated aging showed that alcohol extracts of [i]G. lucidum[/i] contained the main active anti-aging extract. The effects on DNA methylation of these [i]G. lucidum[/i] extracts were then evaluated using SAMP8 and APP/PS1 AD model mice by whole genome bisulfite sequencing, and some methylation regulators including Histone H3, DNMT3A, and DNMT3B in brain tissues were up-regulated after treatment with alcohol extracts from [i]G. lucidum[/i]. Molecular docking analysis was carried out to screen for molecules regulated by specific components, including ganoderic acid Mk, ganoderic acid C6, and lucidone A, which may be active ingredients of [i]G. lucidum[/i], including the methylation regulators of Histone H3, MYT, DNMT3A, and DNMT3B. Auxiliary tests also demonstrated that [i]G. lucidum[/i] alcohol extracts could improve learning and memory function, ameliorate neuronal apoptosis and brain atrophy, and down-regulate the expression of the AD intracellular marker, Aβ . We concluded that alcohol extracts from [i]G. lucidum[/i], including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression.
Keywords
- Alzheimer’s disease
- DNA methylation
- Ganoderma lucidum
- active ingredients
- aging
The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of the present study was therefore to investigate the inter-individual variation in complement activity and the influences of age and sex. Complement levels and functional activity were determined in 120 healthy volunteers, 60 women, 60 men, age range 20-69 year. Serum functional activity of the classical pathway (CP), lectin pathway activated by mannan (MBL-LP) and alternative pathway (AP) was measured in sera, using deposition of C5b-9 as readout. In addition, levels of C1q, MBL, MASP-1, MASP-2, ficolin-2, ficolin-3, C2, C4, C3, C5, C6, C7, C8, C9, factor B, factor D, properdin, C1-inhibitor and C4b-binding protein, were determined. Age- and sex-related differences were evaluated. Significantly lower AP activity was found in females compared to males. Further analysis of the AP revealed lower C3 and properdin levels in females, while factor D concentrations were higher. MBL-LP activity was not influenced by sex, but MBL and ficolin-3 levels were significantly lower in females compared to males. There were no significant differences in CP activity or CP components between females and males, nevertheless females had significantly lower levels of the terminal components. The CP and AP activity was significantly higher in the elderly, in contrast to MBL-LP activity. Moreover, C1-inhibitor, C5, C8, and C9 increased with age in contrast to a decrease of factor D and C3 levels. In-depth analysis of the functional activity assays revealed that MBL-LP activity was predominantly dependent on MBL and MASP-2 concentration, whereas CP activity relied on C2, C1-inhibitor and C5 levels. AP activity was strongly and directly associated with levels of C3, factor B and C5. This study demonstrated significant sex and age-related differences in complement levels and functionality in the healthy population. Therefore, age and sex analysis should be taken into consideration when discussing complement-related pathologies and subsequent complement-targeted therapies.
MeSH Terms
- Adult
- Aged
- Aging
- Complement Activation
- Complement System Proteins
- European Continental Ancestry Group
- Female
- Humans
- Male
- Middle Aged
- Sex Characteristics
Keywords
- complement
- gender
- health
- innate imunity
- sex and age
To investigate the bone mineral density (BMD) of cervical vertebrae in a population-stratified manner and correlate with that of the lumbar vertebrae. Five hundred and ninety-eight healthy volunteers (254 males, 344 females), ranging from 20 to 64 years of age, were recruited for volumetric BMD (vBMD) measurements by quantitative computed tomography. Basic information (age, height, weight, waistline, and hipline), and vBMD of the cervical and lumbar vertebrae (C2-7 and L2-4) were recorded. Comparisons among sex, age groups and different levels of vertebrae were analyzed using analysis of variance. Linear regression was performed for relevance of different vertebral levels. The vBMD of cervical and lumbar vertebrae was higher in females than males in each age group. The vBMD of the cervical and lumbar vertebrae in males and the vBMD of lumbar vertebrae in females decreased with aging. In each age group, the vBMD of the cervical vertebrae was higher than that of the lumbar vertebrae with gradual decreases from C2 to C7 except for C3; moreover, the vBMD of C6 and C7 was significantly different from that of C2-5. Correlations of vBMD among different cervical vertebrae (females: r = 0.62-0.94; males: r = 0.63-0.94) and lumbar vertebrae (males: r = 0.93-0.98; females: r = 0.82-0.97) were statistically significant at each age group. The present study provided normative data of cervical vertebrae in an age- and sex-stratified manner. Sex differences in vBMD prominently vary with age, which can be helpful to design a more comprehensive pre-operative surgical plan.
MeSH Terms
- Adult
- Aging
- Anthropometry
- Asian Continental Ancestry Group
- Bone Density
- Cervical Vertebrae
- Female
- Humans
- Linear Models
- Lumbar Vertebrae
- Male
- Middle Aged
- Reference Values
- Sex Characteristics
- Tomography, X-Ray Computed
- Young Adult
Keywords
- Bone density
- Cervical
- Computed tomography
- Lumbar
- Normal
- Population
- Quantitative
- Vertebra
This cross-sectional study was conducted on the skeletal remains of individuals of known sex, age, and ethnic origin. The vertebral bodies of levels C3-C7 were measured and analyzed. Whereas many studies were performed on the size and shape of the vertebral bodies in the thoracic and lumbar spines, few have focused on the cervical vertebral bodies. Thus, there is insufficient data in the literature on the anatomy of the cervical spine, especially based on large study populations. To establish a large database on cervical vertebral bodies' size and shape and analyze their association with demographic parameters. The population studied was composed of 277 individuals, adult males and females of African American (AA) and European American (EA) origin. The skeletal remains are housed at the Hamman-Todd Osteological collection (Cleveland Museum of Natural History, Cleveland, OH). A 3-D digitizer was used to measure the size and shape of the C3-C7 vertebral bodies. Descriptive statistics were carried out for all measurements. t Test and one-way analysis of variance were performed to assess differences in vertebral bodies' size and shape between different demographical groups (by age, sex, and ethnicity). The vertebral bodies and foramina are significantly wider, more elongated, and higher in males compared to females. AA females and males manifest significantly greater vertebral bodies (width and length) in the upper and midcervical region (vertebrae C3-C5) than EA females and males. Nevertheless, the heights of the C3 and C4 vertebral bodies are significantly smaller among the AA population, regardless of sex. The vertebral foramina's width does not differ significantly between the two ethnic groups, independent of sex, whereas they tend to be elongated in the EA group (significant for C3, C5, C7). For most vertebrae, no significant differences were found in the superior facets' length between AA and EA males and females. Cervical vertebral bodies become wider and more elongated with age, although the changes in the latter dimension are much more pronounced than in the former. Notably, the body shape of the cervical vertebrae changes gradually from a more round shape (C3 length/width index=0.84) to a more oval one (C7 length/width index =0.65). This is due to the fact that the width dimensions increase by almost 40% from C3 to C7, whereas the length dimensions increase only by approximately 10%. Furthermore, there is a significant reduction in body height with age in C3-C6. In contrast, no significant changes in vertebral foramen size with age were found. The cervical vertebral bodies' shape and size are sex-dependent phenomena, that is, in all parameters studied, the dimensions were greater in males than in females. For the midcervical level, there is a difference in body shape between individuals of different ethnic origins. The cervical vertebral bodies also exhibit considerable size and shape changes with age, that is, they become more elongated (oval shaped), wider, and shorter. In contrast, vertebral foramen size is age independent.
MeSH Terms
- Adult
- African Americans
- Body Height
- Cervical Vertebrae
- Cross-Sectional Studies
- European Continental Ancestry Group
- Female
- Humans
- Lumbar Vertebrae
- Male
- Middle Aged
- Organ Size
Keywords
- Aging
- Cervical spine
- Skeletal study
- Spinal anatomy
- Vertebral body
- Vertebral foramen
Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 µg/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2'-deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 μg/kg, when compared to naïve and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Behavior, Animal
- Benzo(a)pyrene
- DNA Damage
- Female
- Hippocampus
- Lipid Peroxidation
- Neurons
- Oxidative Stress
Cross-Sectional Cohort Study OBJECTIVE.: To describe age-stratified normative values of novel occipitocervical, cervical, and cervicothoracic alignment parameters. Full-body radiographic images obtained without stitching or vertical distortion represent an ideal method to evaluate occipitocervical alignment and horizontal gaze. One hundred twenty adults with no back or neck symptoms were recruited. Age, sex, body mass index, Neck Disability Index (NDI), and Oswestry Disability Index scores were recorded. Radiographic parameters measured included: center sacral vertebral line, chin brow vertical angle (CBVA), orbital tilt (OrT), orbital slope, occipital slope (OS), occipital incidence, occiput-C2 (O-C2) lordosis, cervical lordosis (C2-C7, CL), T1 slope (TS), neck tilt, thoracic inlet angle (TIA), cervicothoracic kyphosis (C6-T4), and C2-C7 sagittal vertical axis (C2-7 SVA). Interobserver reliability was calculated for all measurements (intraclass correlation coefficient, ICC). A Pearson correlation was used to determine relationships between variables. A total of 115 patients were analyzed; average age as 50.1 years (range 22-78). All measured variables had an ICC >0.6. CL (r = -0.33, P < 0.001), TS (r = 0.42, P < 0.001), TIA (r = 0.24, P = 0.010), and C7 SVA (r = 0.48, P < 0.001) all increased with age. OrT (r = -0.88, P < 0.001) and OS (r = 0.73, P < 0.001) were both strongly correlated with CBVA and each other (r = -0.83, P ≤ 0.001). Both measures were also correlated with the C2-C7 SVA (OrT, r = 0.41, P < 0.001; OS, r = -0.29, P = 0.002) and O-C2 angle (OrT, r = 0.46, P < 0.001; OS, r = -0.28, P = 0.003). C6-T4 angulations was negatively correlated with NDI scores in this population (r = -0.25, P = 0.007). We present age-based normative values for occipitocervical, cervicothoracic, and cervical alignment parameters using a novel biplanar radiographic imaging technique. We introduce measures of craniocervical alignment that might provide surgeons with an intuitive way to account for the position of the orbit when planning cervical deformity correction. 4.
MeSH Terms
- Adult
- Aged
- Aging
- Cervical Vertebrae
- Cross-Sectional Studies
- Female
- Humans
- Kyphosis
- Lordosis
- Male
- Middle Aged
- Prospective Studies
- Radiography
- Reproducibility of Results
- Thoracic Vertebrae
- Young Adult
Objectives To assess the relationship between cross-sectional area of internal jugular veins and brain volumes in healthy individuals without neurologic disease. Methods A total of 193 healthy individuals without neurologic disease (63 male and 130 female; age > 20 to < 70 years) received magnetic resonance venography and structural brain magnetic resonance imaging at 3T. The internal jugular vein cross-sectional area was assessed at C2-C3, C4, C5-C6, and C7-T1. Normalized whole brain volume was assessed. Partial correlation analyses were used to determine associations. Results There was an inverse relationship between normalized whole brain volume and total internal jugular vein cross-sectional area (C7-T1: males r = -0.346, p = 0.029; females r = -0.301, p = 0.002). After age adjustment, association of normalized whole brain volume and normalized gray matter volume with internal jugular vein cross-sectional area became positive in males (normalized whole brain volume and right internal jugular vein cross-sectional area (C2-C3) changed from r = -0.163 to r = 0.384, p = 0.002), but not in the females. Conclusion Sex differences exist in the relationship between brain volume and internal jugular vein cross-sectional area in healthy individuals without neurologic disease.
MeSH Terms
- Adult
- Aging
- Atrophy
- Brain
- Female
- Humans
- Jugular Veins
- Magnetic Resonance Angiography
- Male
- Middle Aged
- Prospective Studies
Keywords
- Healthy individuals without neurologic disease
- aging
- brain atrophy
- internal jugular veins
- magnetic resonance imaging
- magnetic resonance venography
- sex
Cervical spondylosis is well accepted as a common degenerative change in the cervical spine. Compelling evidence has shown that the incidence of cervical spondylosis increases with age. However, the relationship between age and the incidence of cervical spondylosis remains obscure. It is essential to note the relationship between age and the incidence of cervical spondylosis through more and more clinical data. In the case-controlled study reported here, retrospective clinical analysis of 1,276 cases of cervical spondylosis has been conducted. We analyzed the general clinical data, the relationship between age and the incidence of cervical spondylosis, and the relationship between age-related risk factors and the incidence of cervical spondylosis. A chi-square test was used to analyze the associations between different variables. Statistical significance was defined as a P-value of less than 0.05. The imaging examination demonstrated the most prominent characteristic features of cervical spondylosis: bulge or herniation at C3-C4, C4-C5, and C5-C6. The incidence of cervical spondylosis increased with aging before age 50 years and decreased with aging after age 50 years, especially in the elderly after 60 years old. The occurrence rate of bulge or herniation at C3-C4, C4-C5, C5-C6, and C6-C7 increased with aging before age 50 years and decreased with aging after age 50 years, especially after 60 years. Moreover, the incidence of hyperosteogeny and spinal stenosis increased with aging before age 60 years and decreased with aging after age 60 years, although there was no obvious change in calcification. The age-related risk factors, such as hypertension, hyperlipidemia, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking, have no relationship with the incidence of cervical spondylosis. A decreasing proportion of cervical spondylosis with aging occurs in the elderly, while the proportion of cervical spondylosis increases with aging in the young and the adults. This investigation implicates that aging is not only a contributor to the clinical performance of cervical spondylosis in the elderly, although the incidence of cervical spondylosis is proportional to the progress of age.
MeSH Terms
- Adult
- Age Distribution
- Aged
- Aged, 80 and over
- Aging
- Case-Control Studies
- Cervical Vertebrae
- China
- Female
- Hospitals
- Humans
- Incidence
- Male
- Middle Aged
- Retrospective Studies
- Risk Factors
- Sex Distribution
- Spondylosis
Keywords
- aging
- cervical spondylosis
- incidence
- risk factor
B cell CLL/lymphoma 11B (Bcl11b), a C2H2 zinc finger transcription factor, not only serves as a critical regulator in development but also plays the controversial role in T cell acute lymphoblastic leukemia (T-ALL). We previously found that the enriched expression of Bcl11b was detected in high tumorigenic C6 glioma cells. However, the role of Bcl11b in glioma malignancy and its mechanisms remains to be uncovered. In this study, using the lentivirus-mediated knockdown (KD) approach, we found that Bcl11b KD in tumorigenic C6 cells reduced the cell proliferation, colony formation, and migratory ability. The results were further verified using two human malignant glioma cell lines, U87 and U251 cells. A cyclin-dependent kinase inhibitor p21, a known Bcl11b target, was significantly upregulated in tumorigenic C6, U87, and U251 cells after Bcl11b KD. Cellular senescence was observed by examination of the β-galactosidase activity in U87 and U251 cells with Bcl11b KD. Reduced expression of stemness gene Sox-2 and its downstream effector Bmi-1 was also observed in U87 and U251 cells with Bcl11b KD. These results suggest that the ablation of Bcl11b gene expression induced glioma cell senescence. Propidium iodide (PI) staining combined with flow cytometry analysis also showed that Bcl11b KD led to the cell cycle arrest of U87 and U251 cells at the G0/G1 or at the S phase, indicating that Bcl11b is required for glioma cell cycle progression. Together, this is the first study to show that the inhibition of Bcl11b suppresses glioma cell growth by regulating the expression of the cell cycle regulator p21 and stemness-associated genes (Sox-2/Bmi-1).
MeSH Terms
- Animals
- Brain Neoplasms
- Carcinogenesis
- Cell Cycle Checkpoints
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Cellular Senescence
- Cyclin-Dependent Kinase Inhibitor p21
- Down-Regulation
- Gene Expression Regulation, Neoplastic
- Gene Knockdown Techniques
- Glioma
- Humans
- Polycomb Repressive Complex 1
- Rats
- Repressor Proteins
- SOXB1 Transcription Factors
- Tumor Suppressor Protein p53
- Tumor Suppressor Proteins
- Up-Regulation
Keywords
- Bcl11b
- Cell senescence
- Glioma
- Stemness
- p21
The aims of this study were 1) to establish the standard parameters of alignment and total and segmental range of motion (ROM) of the cervical spine in the asymptomatic population, and 2) to identify factors that influence cervical ROM and alignment. The authors measured 636 standard cervical lateral, flexion, and extension plain radiographs of 212 asymptomatic volunteers. The relationship between cervical alignment and total ROM was assessed with simple linear regression. Multivariate linear regression was used to determine the effect of the influential factors on cervical alignment and total and segmental ROM. The mean value for C2-7 cervical alignment was 21.40° ± 12.15°, and the mean value for total ROM was 63.59° ± 15.37°. Sex was a significant factor in cervical alignment, total ROM, and segmental ROM for C2-3 and C5-6 (p < 0.05). Age had a significant negative association with both the total ROM and all of the segmental ROM measurements (p < 0.05). Cervical disc degeneration at the level of interest had a significant negative association with C4-5, C5-6, and C6-7 ROM (p < 0.05). Cervical alignment in female subjects was 2.47° lower than that in male subjects. Total ROM was 3.86° greater in female than in male subjects and decreased 6.46° for each decade of aging. Segmental ROM decreased 1.28° for each decade of aging and 2.26° for each category increase in disc degeneration at the level of interest.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Biomechanical Phenomena
- Cervical Vertebrae
- Female
- Humans
- Intervertebral Disc
- Intervertebral Disc Degeneration
- Intervertebral Disc Displacement
- Male
- Middle Aged
- Range of Motion, Articular
- Sex Factors
- Young Adult
Keywords
- ICC = intraclass correlation coefficient
- ROM = range of motion
- cervical alignment
- cervical range of motion
- cervical spine
- degenerative
- disc degeneration
- influential factors
The V2 segment of the vertebral artery (VA) ascends and passes through the transverse foramen (TF) of the C6-C1 vertebrae. Atherosclerosis of the VA and degenerative changes in the cervical spine are likely to occur with aging, and subsequent morphologic changes may alter the normal anatomy. The aim was to determine the morphologic changes of TF and VA in relation to aging. This was a retrospective cross-sectional study. One hundred ten consecutive patients who had undergone computed tomography angiography were included. The subjects were then divided into three groups according to age: Group A, less than 45 years; Group B, from 45 to 65 years; and Group C, older than 65 years. Cases with stenosis and dissection of the VA were excluded from the quantitative analysis. The areas of the VA and TF were measured, and the VA/TF occupation ratio (OR) was calculated accordingly. The presence of VAs tortuosity within the TF was also noted. The TF was larger in the oldest group, but the difference was not statistically significant. There was also no significant statistical difference among the age groups in terms of the VA and VA/TF ORs (p>.05). In the Group C, the rate of overall tortuosity of the VA was 73%, and arterial tortuosity in the TF was 28.6%. In cases with tortuous VA, C6 and C4 TFs were found to be significantly larger. Tortuous VAs tend to be associated with enlargement of C6 and C4 TFs. Knowledge of such changes in the anatomy is crucial during instrumentation used for cervical spine surgeries, to prevent serious complications in patients aged older than 65 years.
MeSH Terms
- Adult
- Aged
- Angiography
- Cervical Vertebrae
- Female
- Humans
- Male
- Middle Aged
- Multidetector Computed Tomography
- Vertebral Artery
Keywords
- Aging
- Anatomy
- Cervical spondylosis
- Cervical vertebrae
- Computed tomography angiography
- Vertebral artery
Reduced cell wall recalcitrance and increased C6 monosaccharide content are desirable traits for future biofuel crops, as long as these biomass modifications do not significantly alter normal growth and development. Mixed-linkage glucan (MLG), a cell wall polysaccharide only present in grasses and related species among flowering plants, is comprised of glucose monomers linked by both β-1,3 and β-1,4 bonds. Previous data have shown that constitutive production of MLG in barley (Hordeum vulgare) severely compromises growth and development. Here, we used spatio-temporal strategies to engineer Arabidopsis thaliana plants to accumulate significant amounts of MLG in the cell wall by expressing the rice CslF6 MLG synthase using secondary cell wall and senescence-associated promoters. Results using secondary wall promoters were suboptimal. When the rice MLG synthase was expressed under the control of a senescence-associated promoter, we obtained up to four times more glucose in the matrix cell wall fraction and up to a 42% increase in saccharification compared to control lines. Importantly, these plants grew and developed normally. The induction of MLG deposition at senescence correlated with an increase of gluconic acid in cell wall extracts of transgenic plants in contrast to the other approaches presented in this study. MLG produced in Arabidopsis has an altered structure compared to the grass glucan, which likely affects its solubility, while its molecular size is unaffected. The induction of cell wall polysaccharide biosynthesis in senescing tissues offers a novel engineering alternative to enhance cell wall properties of lignocellulosic biofuel crops.
MeSH Terms
- Aging
- Cell Wall
- Glucans
- Plant Cells
- Plants, Genetically Modified
- Polysaccharides
Keywords
- CslF6
- bioenergy
- cell wall engineering
- gluconic acid
- mixed-linkage glucan
- senescence-associated promoter
Rat models are commonly used to investigate the pathophysiological pathways and treatment outcomes after spinal cord injury (SCI). The high incidence of fall-induced SCI in older adults has created a need for aging models of SCI in rats to investigate potential age-related differences in SCI severity and outcomes. The aims of this study were to determine the influences of age and vertebral level on the geometries of the cervical spinal cord and spinal column in a rat model. Three young (3 months) and three aged (12 months) Fischer 344 rats were imaged in a high field (7 T) small-animal magnetic resonance imaging system. All spinal cord geometry variables (including depth, width, and axial cross-sectional area) and one spinal canal variable (depth) were significantly larger in the aged specimens by an average of 8.1%. There were main effects of vertebral level on all spinal cord variables and four spinal canal variables with values generally larger at C4 as compared to C6 (average increases ranged from 5.7% to 12.9% in spinal cord measures and 5.4% to 6.8% in spinal canal measures). High inter-rater reliability between two measurers was observed with a mean intraclass correlation of 0.921 and percent difference of 0.9% across all variables measured. This study clearly demonstrates that cervical spinal cord geometry changes between the ages of 3 and 12 months in Fischer 344 rats. This information can aid in the planning and interpretation of studies that use a rat model to investigate the influence of age on cervical SCI.
MeSH Terms
- Age Factors
- Aging
- Animals
- Cervical Cord
- Cervical Vertebrae
- Female
- Magnetic Resonance Imaging
- Rats
- Rats, Inbred F344
- Spinal Cord Injuries
Keywords
- aging
- injury
- rat
- spinal column
- spinal cord
Disc space narrowing, osteophytes, and disc degeneration are common and increase with aging. Few animal models are appropriate for the study of spontaneous age-related cervical disc degeneration. We used the sand rat, a member of the gerbil family with well-recognized age-related lumbar disc degeneration, to determine whether spontaneous cervical disc degeneration differed from lumbar degeneration when evaluated by (1) radiologic and (2) histologic measures. Animals 2 to 25 months of age were used in these analyses. Cervical and lumbar discs of 99 sand rats were analyzed with radiology, and cervical discs of 67 sand rats were studied with histology. Lateral digital radiographs of cervical and lumbar spines were scored for presence or absence of wedging, disc space narrowing, osteophytes, end plate calcification, and irregular disc margins at C2-C3 through C6-C7 and T12-L1 through L7-S1. Percentages for presence were calculated and statistically analyzed for younger (range, 2-11.9 months old) versus older (range, 12.0-25 months old) animals. Cervical discs in younger animals exhibited a greater proportion of irregular margins compared with lumbar sites (94% versus 83%; p = 0.02; 95% CI for difference, 2.7, 19.0%). In older animals, cervical discs showed a greater proportion of osteophytes than did lumbar discs (7% versus 0%; p < 0.0001). The incidence of disc space narrowing was greater in cervical versus lumbar sites (99% versus 90%; p = 0.0008). Cervical spine sites which contained osteophytes morphologically showed irregular disc margins and revealed an extrusion of herniated disc material in the osteophytes. Radiologic and morphologic studies confirmed age-related disc degeneration in the cervical spine of the sand rat. Clinical cervical aging studies have shown that 14% of asymptomatic subjects younger than 40 years have abnormal MRI scans with an increase to 50% by 50 years old. We studied an economic rodent model for cervical age-related spontaneous disc.
MeSH Terms
- Age Factors
- Aging
- Animals
- Cervical Vertebrae
- Disease Models, Animal
- Female
- Gerbillinae
- Intervertebral Disc Degeneration
- Lumbar Vertebrae
- Male
- Radiography
Growing evidences have revealed that the proforms of several neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3), by binding to p75 neurotrophin receptor and sortilin, could induce neuronal apoptosis and are implicated in the pathogenesis of various neurodegenerative diseases. The glial cell line-derived neurotrophic factor (GDNF), one of the most potent useful neurotrophic factors for the treatment of Parkinson's disease (PD), is firstly synthesized as the proform (proGDNF) like other neurotrophin NGF, BDNF, and NT3. However, little is known about proGDNF expression and secretion under physiological as well as pathological states in vivo or in vitro. In this study, we investigated the expression profile and dynamic changes of proGDNF in brains of aging and PD animal models, with the interesting finding that proGDNF was a predominant form of GDNF with molecular weight of about 36 kDa by reducing and nonreducing immunoblots in adult brains and was unregulated in the aging, lipopolysaccharide (LPS), and 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) insult. We further provided direct evidence that accompanied activation of primary astrocytes as well as C6 cell line induced by LPS stimulation, proGDNF was increasingly synthesized and released as the uncleaved form in cell culture. Taken together, our results strongly suggest that proGDNF may be a biologically active protein and has specific effects on the cells close to its secreting site, and a potentially important role of proGDNF signaling in the brains, in the glia-neuronal interaction or in the pathogenesis of PD, should merit further investigation.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Brain
- Columbidae
- Disease Models, Animal
- Glial Cell Line-Derived Neurotrophic Factor
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Molecular Sequence Data
- Parkinsonian Disorders
- Protein Precursors
- Rats
- Rats, Sprague-Dawley
Head and neck injuries, the leading cause of death for children in the U.S., are difficult to diagnose, treat, and prevent because of a critical void in our understanding of the biomechanical response of the immature cervical spine. The objective of this study was to investigate the functional and failure biomechanics of the cervical spine across multiple axes of loading throughout maturation. A correlational study design was used to examine the relationships governing spinal maturation and biomechanical flexibility curves and tolerance data using a cadaver human in vitro model. Eleven human cadaver cervical spines from across the developmental spectrum (2-28 years) were dissected into segments (C1-C2, C3-C5, and C6-C7) for biomechanical testing. Non-destructive flexibility tests were performed in tension, compression, flexion, extension, lateral bending, and axial rotation. After measuring their intact biomechanical responses, each segment group was failed in different modes to measure the tissue tolerance in tension (C1-C2), compression (C3-C5), and extension (C5-C6). Classical injury patterns were observed in all of the specimens tested. Both the functional (p<0.014) and failure (p<0.0001) mechanics exhibited significant relationships with age. Nonlinear flexibility curves described the functional response of the cervical spine throughout maturation and elucidated age, spinal level, and mode of loading specificity. These data support our understanding of the child cervical spine from a developmental perspective and facilitate the generation of injury prevention or management schema for the mitigation of child spine injuries and their deleterious effects.
MeSH Terms
- Adolescent
- Adult
- Aging
- Biomechanical Phenomena
- Cervical Vertebrae
- Child
- Child, Preschool
- Compressive Strength
- Computer Simulation
- Female
- Humans
- Male
- Stress, Mechanical
- Tensile Strength
- Young Adult