C2
Complement C2 precursor (EC 3.4.21.43) (C3/C5 convertase) [Contains: Complement C2b fragment; Complement C2a fragment]
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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
The honeybee has economic importance both for the commercial value of bee products and for its role in the pollination of agricultural crops. Despite the fact that the fungicides are widely used in agriculture, studies comparing the effects of this group of pesticides on bees are still scarce. There are many gaps preventing the understanding of bees' responses to exposure to fungicides, including the influence of the age of the exposed workers. However, this study aimed to compare the effects of residual concentrations of pyraclostrobin on young and old bees of Africanized Apis mellifera. The parameters analyzed were the survival rates, as well as the histopathological and histochemical changes in midgut of orally exposed workers to different sublethal concentrations of this strobilurin fungicide: 0.125 ng a.i./μL (C1), 0.025 ng a.i./μL (C2) e 0.005 ng a.i./μL (C3). The results showed a significant decrease in the longevity only for old bees exposed to the three concentrations of pyraclostrobin. After the five-day exposure period, the fungicide induced sublethal effects in the midgut only from the old bees. These effects were the increase both in cytoplasmic vacuolization of digestive cells and morphological changes in the nests of regenerative cells, which reflected in the higher lesion index of organ for groups C1 and C2. Additionally, there was a reduction in total protein staining in the intestinal epithelium in C1 and C2. At the same exposure period, the midgut of young bees presented only a reduction in the staining of neutral polysaccharides in the group C1. Concluding, old workers are more sensitive to the fungicide than young workers. This study showed different responses according to worker age, which can affect the maintenance of colony health. Future studies should take into account the age of the workers to better understand the effects of fungicides on bees.
MeSH Terms
- Animals
- Bees
- Fungicides, Industrial
- Insecticides
- Neonicotinoids
- Nitro Compounds
- Strobilurins
Keywords
- Apis mellifera
- Longevity
- Midgut
- Morphophysiology
- Strobilurin fungicide
To investigate the effects of resistance exercise on mitochondrial function in skeletal muscle of aging rats. Forty male Sprague-Dawley rats were randomly assigned to 4 groups, 2-month sedentary control group (C1; [i]n[/i]=10), 2-month with resistance training group (R1; [i]n[/i]=10), 6-month sedentary control group (C2; [i]n[/i]=10), 6-month with resistance training group (R2; [i]n[/i] =10 ). Rats in R1 and R2 groups were arranged for resistance training for 8 weeks. This program consisted of interval running on a treadmill, speed 15 m·min , 35° incline, duration 15 s, interval 30 s, 4 times/group, 3 groups/cycle, 2 cycles per day, 6 days per week, a total of 8 weeks. The expressions of mitochondrial fusion protein 2(Mfn2) and dynamin-related protein 1(DRP1) in rat quadriceps were detected by Western blot, and the changes of mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) and Ca concentration were measured by flow cytometry. ①Compared with C1 group, the expression of DRP1 protein in R1 group was increased ([i]P[/i]＜0. 01), and the Mfn2 protein in R1 group had no significant difference, both DRP1 and Mfn2 protein in C2 group were decreased ([i]P[/i]＜0. 01);compared with C2 group, the DRP1 and Mfn2 protein in R2 group were similarly increased ([i]P[/i]＜0. 01, [i]P[/i]＜0. 05);compared with R1 group, the DRP1 and Mfn2 protein in R2 group were both decreased ([i]P[/i]＜0. 01). ② Compared with C1 group, the Ca content of R1 group was decreased ([i]P[/i]＜0. 01) and the Ca content of C2 group was increased ([i]P[/i]＜0. 01);Compared with C2 group, the content of Ca in R2 group was decreased ([i]P[/i]＜0. 01);compared with R1 group, the Ca content in R2 group was increased ([i]P[/i]＜0. 01). ③ Compared with C1 group, the ROS content in R1 group was increased, but there was no significant difference, while the ROS content in C2 group was increased ([i]P[/i]＜0. 01);compared with C2 group, ROS content in R2 group was decreased ([i]P[/i]＜0. 01); compared with R1 group, the ROS content in R2 group was increased ([i]P[/i]＜0. 01). ④ Compared with group C1, the levels of ΔΨm in C2 group was decreased ([i]P[/i]＜0. 01);Compared with C2 group, The ΔΨm of R2 group was increased([i]P[/i]＜0. 01); Compared with group R1, the ΔΨm of R2 group was decreased, but there was no statistical difference. During the aging process of rats, mitochondria of quadriceps femoral muscle showed Ca accumulation, increased reactive oxygen species, decreased mitochondrial membrane potential, decreased fusion protein and other phenomena, and resistance training could effectively improve these changes.
MeSH Terms
- Aging
- Animals
- Male
- Membrane Potential, Mitochondrial
- Mitochondria, Muscle
- Muscle, Skeletal
- Physical Conditioning, Animal
- Rats
- Rats, Sprague-Dawley
- Resistance Training
Keywords
- fusion protein 2
- mitochondria
- quadriceps
- rats
- resistance training
In the older population, tortuosity of the vertebral artery (VA), uncovertebral joint (UVJ) osteoarthritis, and abnormal vertebral alignment may alter the normal anatomy. We aimed to determine the anatomical variations and relationships between the cervical segment of the VA and the cervical spine with regard to ageing. In this retrospective cross-sectional study, the computed tomography angiography scans of 110 subjects were reviewed. Any variations in the VA, UVJ degeneration were identified. The distance between the VA and uncinate process (UP) was measured electronically. The distance between the VA and UP were compared according to the age group (group A < 45, group B = 45-65, and group C > 65 years-old). With regard to the transverse foramen, 7.2% of the cases had entering abnormalities of the VA, while in one case (0.83%), the right VA had an exiting abnormality (exiting from the C2 instead of the C1). UVJ degeneration was found to be significantly higher in the older age group (p < 0.05). Furthermore, at the C4-C7 levels, the distances between the VA and UP were significantly smaller in the older age group (p < 0.01). The VA-UP distance has been shown to decrease due to increasing UVJ osteoarthritis in the elderly. The convergence of the VA toward the spine occurs at the most mobile segment of the cervical spine, and this anatomical alteration may predispose temporary and/or permanent vertebral artery occlusion clinically, and be dangerous during cervical spine surgery.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Cervical Vertebrae
- Computed Tomography Angiography
- Cross-Sectional Studies
- Female
- Humans
- Male
- Middle Aged
- Retrospective Studies
- Vertebral Artery
Keywords
- angiography
- computed tomography
- osteoarthritis
- spine
- vertebral artery
- aging
Phosphatidylinositol 3-kinases (PI3Ks) are characterized by the presence of a C2 domain at the N-terminal end (class I, III); or at both the N-terminal and C-terminal ends (class II), sometimes including a Plextrin homology domain and/or a Ras domain. Plant PI3Ks are analogous to the class III mammalian PI3K. An N-terminal fragment (~170 aa) of the tomato PI3K regulatory domain including the C2 domain, was cloned and expressed in a bacterial system. This protein was purified to homogeneity and its physicochemical properties analyzed. The purified protein showed strong binding with monophosphorylated phosphatidylinositols, and the binding was dependent on calcium ion concentration and pH. In the overall tertiary structure of PI3K, C2 domain showed unique characteristics, having three antiparallel beta-sheets, hydrophobic regions, acidic as well as alkaline motifs, that can enable its membrane binding upon activation. To elucidate the functional significance of C2 domain, transgenic tobacco plants expressing the C2 domain of PI3K were generated. Transgenic plants showed defective pollen development and disrupted seed set. Flowers from the PI3K-C2 transgenic plants showed delayed wilting, and a decrease in ethylene production. It is likely that introduction of the PI3K-C2 segment may have interfered with the normal binding of PI3K to the membrane, delaying the onset of membrane lipid catabolism that lead to senescence.
MeSH Terms
- Animals
- C2 Domains
- Lycopersicon esculentum
- Phosphatidylinositol 3-Kinase
- Plants, Genetically Modified
- Protein Binding
- Tobacco
Keywords
- C2 domain
- Membrane binding
- Phosphatidylinositol 3-kinase
- Senescence
Antibiotic administration by subcutaneous (SC) injection is common practice in French geriatric wards as an alternative to the intravenous (IV) route, but few pharmacokinetic/pharmacodynamic data are available. Ertapenem is useful for the treatment of infections with ESBL-producing enterobacteria. To report and compare ertapenem pharmacokinetic data between IV and SC routes in older persons. Patients >65 years of age receiving ertapenem (1 g once daily) for at least 48 h (IV or SC, steady-state) were prospectively enrolled. Total ertapenem concentrations [residual (C0), IV peak (C0.5) and SC peak (C2.5)] were determined by UV HPLC. Individual-predicted AUC0-24 values were calculated and population pharmacokinetic analyses were performed. Using the final model, a Monte Carlo simulation involving 10 000 patients evaluated the influence of SC or IV administration on the PTA. Tolerance to ertapenem and recovery were also monitored. ClinicalTrials.gov identifier: NCT02505386. Ten (mean ± SD age=87±7 years) and 16 (age=88±5 years) patients were included in the IV and SC groups, respectively. The mean C0 and C2.5 values were not significantly different between the IV and SC groups (C0=12±5.9 versus 12±7.4 mg/L, P=0.97; C2.5=97±42 versus 67±41 mg/L, P=0.99). The mean C0.5 was higher in the IV group compared with the SC group (C0.5=184±90 versus 51±66 mg/L, P=0.001). The mean individual AUCs (1126.92±334.99 mg·h/L for IV versus 1005.3±266.0 mg·h/L for SC, P=0.38) and PTAs were not significantly different between groups. No severe antibiotic-related adverse effects were noted. SC administration of ertapenem is an alternative to IV administration in older patients.
MeSH Terms
- Administration, Intravenous
- Age Factors
- Aged
- Aged, 80 and over
- Anti-Bacterial Agents
- Enterobacteriaceae Infections
- Ertapenem
- Female
- France
- Geriatrics
- Humans
- Injections, Subcutaneous
- Male
- Monte Carlo Method
- Prospective Studies
Anterior cervical discectomy and fusion (ACDF) is the most commonly performed procedure for degenerative cervical spondylosis. Because of its relatively low invasiveness and surgical procedure, old age is not regarded as an exclusion criterion for ACDF. However, very few studies have been conducted on the radiological and clinical outcomes of ACDF in older patients. The purpose of this study was to evaluate the radiological and clinical outcomes of ACDF in older patients. We retrospectively analyzed 48 patients (> 65 years) who underwent ACDF from January 2011 to December 2015. We divided the patients into 2 groups: young-old age group (65-74 years) and middle-old age group (≥ 75 years). Cervical lateral radiographs taken in the neutral standing position were evaluated preoperatively (PRE), on postoperative day 7 (POST), and at the 1-year follow-up (F/U). The radiological parameters included cervical angle (CA: C2-7 Cobb angle), segmental angle, total intervertebral height, disc height, sagittal vertical axis (SVA), T1 slope (T1s), and range of cervical motion (extension CA minus flexion CA). Postoperative hospital days, comorbidities, complications, and clinical outcomes were also analyzed. We analyzed data from 48 patients (group A: n = 30 patients, 46 segments, mean age, 68.60 ± 3.36 years; group B: n = 18 patients, 23 segments, mean age, 79.22 ± 2.63 years). The surgical levels were as follows: C3/4, 4; C4/5, 7; C5/6, 10; C6/7, 29; and C7/ T1, 6 levels, and there were no significant between-group differences in the distribution. There were no significant between-group differences in the fusion and subsidence rates (fusion rate: group A, 76.2%; group B, 71.4%; p = 0.732; subsidence rate: group A, 34.8%; group B, 26.1%; p = 0.587). There was no longitudinal trend in the repeated-measurements analysis of variance test of the 2 groups of the PRE, POST, and F/U data for each radiological parameter. According to the paired t-test, T1 slope (T1s), SVA, and CA did not differ preoperatively and postoperatively. There was no statistically significant difference in visual analogue scale scores (axial, arm), the Neck Disability Index, or Odom's criteria between the 2 groups (p = 0.448, p = 0.357, and p = 0.913). There was no significant difference in radiological and clinical outcomes between young-old and middle-old patients. Middle-old age does not seem to be a limitation to ACDF, but larger-scale and longer-term studies are needed to confirm the findings of this study.
Keywords
- Cervical vertebrae
- Geriatrics
- Postural balance
- Spinal fusion
Hereditary Parkinson's disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the autosomal recessive deficiency of PINK1 Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of PINK1-knockout with overexpression of SNCA in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As an exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in MAP1B, a microtubule-associated protein, and a similar reduction of phosphoSer3781 in ANK2, an interactor of microtubules. MAP1B depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension, and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was also detected for other microtubule and microfilament factors, namely MAP2 , MARK1 , MAP1A , KIF1A , 4.1N , 4.1G , and ADD2 . While the MAP1B heavy chain supports regeneration and growth cones, its light chain assists DAPK1-mediated autophagy. Interestingly, relevant phosphorylation decreases of DAPK2 , VPS13D , and VPS13C in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM C2 domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of ANK2/MAP1B expression on PINK1 levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that MAP1B/ANK2 phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in [i]Drosophila melanogaster[/i] that the MAP1B ortholog futsch in the presynapse is a primary target of the PARK8 protein LRRK2, and on a report that MAP1B is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, [i]ANK2[/i] gene locus variants are associated with the risk of PD, ANK2 interacts with PINK1/Parkin-target proteins such as MIRO1 or ATP1A2, and ANK2-derived peptides are potent inhibitors of autophagy.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Ankyrins
- Autophagy
- Brain
- Mice, Knockout
- Mice, Mutant Strains
- Microtubule-Associated Proteins
- Microtubules
- Phosphoproteins
- Phosphorylation
- Phosphoserine
- Phosphothreonine
- Protein Domains
- Protein Kinases
- Proteome
- Synapses
- alpha-Synuclein
Keywords
- PINK1
- Parkinson’s disease
- alpha-synuclein
- autophagy
- brain phosphorylome
- microtubular cytoskeleton
- synaptic signaling
Retrospective cohort study. To identify age-related changes in cervical sagittal parameters using standard radiographs. Cervical sagittal balance is important for the maintenance of neutral head posture and horizontal gaze. Degenerative changes in the cervical spine that occur with aging may alter cervical sagittal balance, which can lead to chronic neck pain and predispose to various cervical spine pathologies. We performed a retrospective cohort study of 151 patients with lateral cervical spine radiographs taken at our institution between December 2017 and June 2018. Cervical sagittal parameters were measured, including C1 inclination, C2 slope, C2-C7 Cobb angle, cervical sagittal vertical axis (cSVA), cervical tilt, upper and lower C7 slopes, T1 slope, and T1 slope minus cervical lordosis (TS-CL). The association between age and cervical sagittal parameters was assessed using the Pearson correlation coefficient and a linear regression analysis. An analysis of variance (ANOVA) with Tukey adjustments was then performed to identify differences in cervical sagittal parameters among patients aged 18 to 39 years, 40 to 64 years, and >64 years of age. There were positive correlations between age and C2-C7 Cobb angle (r = 0.231, P = 0.004), upper C7 slope (r = 0.280, P < 0.001), lower C7 slope (r = 0.283, P < 0.001), and T1 slope (r = 0.189, P = 0.020). Upper C7 slope (R = 0.079) and lower C7 slope (R = 0.074) had the strongest correlation with age in the linear regression analysis. The ANOVA found significant differences among the age subgroups in terms of C2-C7 Cobb angle (P = 0.002), upper C7 slope (P < 0.001), lower C7 slope (P < 0.001), and T1 slope (P = 0.031). Patients >64 years old had significantly higher C2-C7 Cobb angle, upper C7 slope, lower C7 slope, and T1 slope. Changes in cervical sagittal alignment with age are characterized by increased cervical lordosis and increased thoracic kyphosis. 3.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Cervical Vertebrae
- Humans
- Kyphosis
- Lordosis
- Middle Aged
- Retrospective Studies
- Young Adult
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
A 20-year longitudinal study. To evaluate the long-term effect of sagittal alignment of the cervical spine on intervertebral disk degeneration in healthy asymptomatic subjects. This study continues a previous 10-year longitudinal study to determine whether sagittal alignment affects disk degeneration during normal aging. We assessed 90 healthy subjects (30 men and 60 women) from among 497 volunteers who underwent magnetic resonance imaging (MRI) and plain radiographs of the cervical spine between 1994 and 1996 (follow-up rate 18.1%). The mean age at the initial study was 35.5±13.4 years (11-65 y). We compared initial MRIs and follow-up MRIs, conducted at an average of 21.6 years after the initial study, for (1) decreased signal intensity of the intervertebral disks, (2) posterior disk protrusion, and (3) disk-space narrowing from C2-3 to C7-T1. Subjects were grouped by age at follow-up (under 40 vs. 40 y and older) and by a lordotic or nonlordotic cervical sagittal alignment at baseline. We assessed neck pain, stiff shoulders, and upper-arm numbness at follow-up, and examined associations between clinical symptoms and MRI parameters. Progressive changes during the 20-year period included a decrease in disk signal intensity (84.4% of subjects), posterior disk protrusion (86.7%), and disk-space narrowing (17.8%). No significant association was observed between sagittal alignment and decreased disk signal intensity, posterior disk protrusion, or disk-space narrowing. Among subjects over the age of 40, progressive degenerative changes at C7-T1 were significantly more frequent in nonlordotic subjects (90.9%) compared with those with cervical lordosis (54.2%, P=0.032). The prevalence of clinical symptoms was similar in lordotic and nonlordotic subjects at follow-up. Nonlordotic cervical alignment was related to the progression of disk degeneration at C7-T1 but not other levels. Cervical alignment did not affect the development of clinical symptoms in healthy subjects. Level III.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Cervical Vertebrae
- Child
- Female
- Follow-Up Studies
- Humans
- Intervertebral Disc Degeneration
- Longitudinal Studies
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Posture
- Survivors
- Young Adult
Dialdehyde cellulose (DAC) derived from α-cellulose by periodate oxidation was solubilized and utilized as a suitable crosslinking agent for poly(vinyl alcohol) (PVA). The crosslinking occurs between reactive aldehyde groups of DAC on the C2 and C3 carbons of anhydroglucose unit and hydroxyl groups on PVA backbone in the presence of acidic catalyst. Two catalyst systems based on diluted hydrochloric or sulfuric acid were tested. Their influence on the PVA/DAC network has been investigated by solid-state C NMR, XRD analysis and in the terms of network parameters and mechanical properties. Because DAC undergoes structural changes and decays with time, the role of DAC solution age (1, 14 and 28 days old) on material properties of formed PVA/DAC samples was studied as well. Outlined, even after 28 days after solution preparation, DAC exhibited the capability to act as an efficient crosslinker for PVA. The resulting material properties of PVA/DAC hydrogels were found to be dependent on the molecular weight of solubilized DAC closely related to its age and the choice of catalyst system. Furthermore, the DAC potential for PVA crosslinking was investigated in a broad concentration range. Besides, the DAC crosslinking efficiency was also compared to that of common crosslinking agent glutaraldehyde. The results showed different network topology of prepared hydrogels and exceptional crosslinking potential of DAC in comparison to glutaraldehyde, which is most likely related to DAC macromolecular character.
Keywords
- Aging
- Crosslinking
- Dialdehyde cellulose
- Glutaraldehyde
- Network parameters
- Poly(vinyl alcohol)
This retrospective in-vitro study investigated tooth age effect on dental hard-tissue conditions. Unidentified extracted premolars (n = 1500) were collected and their individual age was estimated (10-100 (±10) years old (yo)) using established dental forensic methods Dental caries, fluorosis and tooth wear (TW) were assessed using the International Caries Detection and Assessment System (ICDAS; 0-5 for crown and 0-2 for root), Thylstrup-Fejerskov (TFI; 0-9) and Basic Erosive Wear Examination (BEWE; 0-3) indices, respectively. Staining and color were assessed using the modified-Lobene (MLI) (0-3) and VITA shade (B1-C4) indices, respectively. Relationships between indices and age were tested using regression models. Starting at age ∼10yo, presence of caries increased from 35% to 90% at ∼50yo (coronal), and from 0% to 35% at ∼80yo (root). Caries severity increased from ICDAS 0.5 to 2 at ∼40yo and from ICDAS 0 to 0.5 at ∼60yo for coronal and root caries, respectively. Presence of TW increased from 25% (occlusal) and 15% (smooth-surfaces) to 100% at ∼80yo. TW severity increased from BEWE 0.5 to 2 at ∼50yo (occlusal) and ∼0.3 to 1.5 at ∼50yo (smooth-surfaces). Percentage and severity of fluorosis decreased from 70% to 10% at ∼80yo, and from TFI 1 to 0 at ∼90yo, respectively. Percentage of extrinsic staining increased from 0% to 85% at ∼80yo and its severity increased from MLI 0 to 2 at ∼70yo. Color changed from A3 to B3 at ∼50yo (crown), and from C2 to A4 at ∼85yo (root). Aging is proportionally related to the severity of caries, TW, staining, and inversely to dental fluorosis. Teeth become darker with age.
MeSH Terms
- Adolescent
- Adult
- Age Determination by Teeth
- Aged
- Aged, 80 and over
- Aging
- Bicuspid
- Child
- Color
- Dental Caries
- Dental Enamel
- Dentin
- Female
- Fluorosis, Dental
- Forensic Dentistry
- Hardness
- Humans
- Male
- Middle Aged
- Retrospective Studies
- Tooth Crown
- Tooth Diseases
- Tooth Wear
- Young Adult
Keywords
- Aging
- Caries
- Dentin
- Enamel
- Fluorosis
- Tooth color
- Tooth wear
Niemann-Pick type C2 (NPC2) disease is a rare, neurodegenerative disorder caused by mutations in the NPC2 gene, leading to lysosomal accumulation of unesterified cholesterol and other lipids. It is characterized by hepatosplenomegaly, liver dysfunction and severe neurological manifestations, resulting in early death. There is no effective therapy for NPC2 disease. Here, we evaluated the effectiveness of an adeno-associated virus (AAV), serotype rh.10 gene transfer vector expressing the mouse Npc2 gene (AAVrh.10-mNpc2-HA, HA tagged to facilitate analysis) to treat the disease in an Npc2-/- mouse model. A single intracisternal administration of the AAVrh.10-mNpc2-HA to 6 week old Npc2-/- mice mediated vector DNA, transgene mRNA and protein expression in brain and other organs. Compared to untreated Npc2-/- mice, AAV-treated Npc2-/- mice demonstrated amelioration of disease pathology in the brain, reduced lysosomal storage, reduced Purkinje cell death, decreased gliosis, and improved performance in behavioral tasks. Treatment-related reduction in serum disease markers was detected early and this effect persisted. Liver and spleen pathology were improved with significant reduction of liver cholesterol and sphingomyelin levels in treated Npc2-/- mice. Finally, administration of AAVrh.10-mNpc2-HA significantly extended life-span. Taken together, these data demonstrate the benefit of a one-time intracisternal administration of AAVrh.10-mNpc2-HA as a life-long treatment for NPC2 disease.
MeSH Terms
- Animals
- Cisterna Magna
- Dependovirus
- Gene Expression
- Genetic Therapy
- Genetic Vectors
- Life Expectancy
- Liver
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Microinjections
- Motor Activity
- Niemann-Pick Disease, Type C
- Phenotype
- Psychomotor Performance
- Spleen
- Vesicular Transport Proteins
Keywords
- AAVrh.10 gene therapy
- Correction of neurologic and systemic manifestations
- Intracisternal delivery
- Niemann pick type C
- Niemann pick type C2 disease
- Single administration
Dietary restriction is one of the several ways which could putatively extend organisms' lifespan, ranging from Saccharomyces cerevisiae to rodents, by activating the AMP-activated protein kinase (AMPK), an ATP/AMP sensor. Extensive researches have shown that aging reduces sensibility of AMPK and eventually causes energy imbalance in cells. Research in mammals' AMPK depicts that this signaling molecule could control autophagy, improve cellular stress resistance and suppress inflammatory responses. Hence, in this study we performed a drug repurposing of 1908 FDA-approved drugs in order to discover putative safe activators of AMPK and to find new applications for existing drugs. For this purpose, FDA-approved drugs were screened by virtual screening and the ligand-protein interactions were carefully inspected. Moreover, through MM/PBSA analysis, the binding affinity of hit compounds in γ and αβ binding sites were investigated. As Cangrelor, Nacitentan, Levoleucovorin and Glisoxepide had lower binding affinities; we predicted that they would probably prove to be more potential activators than C2. However, hit-compounds in αβ binding site, exhibited higher unfavorable binding affinity. Hence, present findings can prove to be valuable for discovering new activators for AMPK.
MeSH Terms
- Adenylate Kinase
- Animals
- Catalytic Domain
- Computer-Aided Design
- Drug Design
- Drug Discovery
- Drug Evaluation, Preclinical
- Drug Repositioning
- Enzyme Activation
- Humans
- Hydrogen Bonding
- Ligands
- Longevity
- Molecular Docking Simulation
- Molecular Dynamics Simulation
- United States
- United States Food and Drug Administration
- User-Computer Interface
Keywords
- AMPK
- Drug repurposing
- FDA-approved drugs
- Virtual screening
A cross-sectional study. To investigate the correlation of cervical spine alignment changes with aging in asymptomatic population. Previous studies demonstrated the influence of lumbar and thoracic spine on cervical spine alignment, but few has reported the cervical spine alignment change along with aging in asymptomatic population. Asymptomatic population were divided into four groups according to different ages (Group A: ≤20 years; Group B: 21-40 years; Group C: 41-60 years; Group D: ≥61 years). Each group was composed of 30 subjects. The following parameters were measured: C0-1 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, C1-7 sagittal vertical axis (C1-7 SVA), C2-7 SVA, central of gravity to C7 sagittal vertical axis (CG-C7 SVA), Thoracic Inlet Angle (TIA), Neck Tilt (NT), cervical tilt, cranial tilt, T1 slope (TS), TS-CL, and ANOVA statistical method was used to analyze the differences among four groups, and then, linear regression analysis was performed to analyze correlation of the cervical spine alignment with the aging. C1-7 SVA, C2-7 SVA, CG-C7 SVA, TIA, NT, TS, and cranial tilt were found statistically different among four groups (P < 0.01). From Group A to Group D, the mean C1-7 SVA were 30.7, 26.0, 21.8, and 36.9 mm, the mean C2-7 SVA were 18.7, 14.7, 11.9, and 24.7 mm, and the mean CG-C7 SVA were 19.6, 16.6, 9.4, and 26.7 mm. The mean TIA were 62.4°, 65.0°, 71.8°, and 76.9°, the mean NT were 39.4°, 43.8°, 46.3°, and 48.2°, the mean TS were 23.0°, 21.1°, 25.5°, and 28.7°, and the mean cranial tilt were 5.7°, 4.8°, 3.0°, and 9.5°. Further linear regression indicated that TIA (r = 0.472; P < 0.0001), NT (r = 0.337; P = 0.0006), and TS (r = 0.299; P = 0.0025) were positively correlated with aging. A gradual increase of TIA, NT, and TS, accompanied with an increased CL, is found along with aging in asymptomatic population, among which TIA, NT, and TS are significantly correlated with physiological nature of aging.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cervical Vertebrae
- Child
- Cross-Sectional Studies
- Disability Evaluation
- Female
- Humans
- Male
- Middle Aged
- Neck
- Radiography
- Skull
- Young Adult
Keywords
- Aging
- Asymptomatic population
- Cervical spine alignment
- Radiology
Pattern onset VEPs do not always show distinct C1-C2-C3 peaks and troughs. Our purpose was to study changes in pattern onset VEP with age to determine when the illustrated ISCEV standard onset VEP waveform can be reliably recorded. We recorded pattern onset VEPs from an Oz electrode referred to mid-frontal electrode according to ISCEV standards by presenting checks of 60' and 15' side length in a 15° field. Twenty-four adults aged 20-63 years participated. Amplitudes and latencies were collated. Pattern onset adult VEP shapes were compared to the waveform published in the ISCEV VEP standard and to paediatric pattern onset VEP waveforms recorded from 16 infants aged 7 months. The shape of the pattern onset VEP changed gradually with age. The C1-C2-C3 morphology of the ISCEV standard pattern onset VEP becomes apparent consistently after 40 years to 60' check stimulation. As age increases a negative trough, C2 is more frequently seen; however, the broad positive peak which characterises infant onset VEPs may still be recorded at 20 years. The group median measurements of onset VEPs to 60' were C1 7 µV@ 88 ms (range 67-110 ms), C2 9 µV@109 ms (range 89-158 ms) and C3 13 µV@121-246 ms. To smaller 15' checks, peak latencies were earlier and C2 became more obvious. The group median measures of onset VEPs to 15' were C1 2 µV@69 ms (55-108 ms), C2 10 µV@90 ms (77-145 ms) and C3 14 µV@122 ms (99-200 ms). The ISCEV standard onset VEP best describes the waveform configuration and latency of the onset VEP produced by 60' checks in adults of more than 40 years of age. The onset VEP waveform produced by 15' checks is distinguished by more prominent negative C2 and earlier C1 and C2 latencies.
MeSH Terms
- Adult
- Aging
- Cross-Sectional Studies
- Electrophysiology
- Evoked Potentials, Visual
- Female
- Humans
- Infant
- Male
- Middle Aged
- Ophthalmology
- Retrospective Studies
- Societies, Medical
- Young Adult
Keywords
- Age
- Check size
- ISCEV standard VEP waveform
- Pattern onset VEP
- Waveform maturation
A comprehensive understanding of normative sagittal profile is necessary for adult spinal deformity. Roussouly described four sagittal alignment types based on sacral slope, lumbar lordosis, and location of lumbar apex. However, the lower limb, a newly described component of spinal malalignment compensation, is missing from this classification. This study aims to propose a full-body sagittal profile classification in an asymptomatic population based on full-body imaging. This is a retrospective analysis of a prospective single-center study of 116 asymptomatic volunteers. Cluster analysis including all sagittal parameters was first performed, and then ANOVA was performed between sub-clusters to eliminate the non-significantly different parameters. This loop was repeated until all parameters were significantly different between each sub-cluster. Three types of full-body sagittal profiles were finalized according to cluster analysis with ten radiographic parameters: hyperlordosis type (77 subjects), neutral type (28 subjects), and compensated type (11 subjects). Radiographic parameters included knee angle, pelvic shift, pelvic angle, PT, PI-LL, C7-S1 SVA, TPA, T1 slope, C2-C7 angle, and C2-C7 SVA. Age was significantly different across compensation types, while BMI and gender were comparable. Age-matched subjects were randomly selected with 11 subjects in each type. ANOVA analysis revealed that all parameters but PT and C2-C7 angle remained significantly different. The current three compensation types of full-body sagittal profiles in asymptomatic adults included significant changes from cervical region to knee, indicating that subjects should be evaluated with full-length imaging. All three types exist regardless of age, but the distribution may vary.
MeSH Terms
- Adult
- Aged
- Aging
- Cluster Analysis
- Female
- Humans
- Knee Joint
- Lower Extremity
- Lumbar Vertebrae
- Male
- Middle Aged
- Pelvic Bones
- Prospective Studies
- Radiography
- Retrospective Studies
- Spine
- Young Adult
Keywords
- Asymptomatic volunteers
- Full-body profile
- Lower limbs
- Sagittal alignment
Complement C1 is the defining component of the classical pathway. Within the C1qC1r C1s complex, C1q functions as a molecular scaffold for C1r C1s and C1q binding to its ligands activates these two serine proteases. The classic C1q ligands are antigen-bound antibodies and activated C1s cleaves C4 and C2 to initiate the complement cascade. Recent studies suggest broad C1 functions beyond the complement system. C1q binds to the Frizzled receptors to activate C1s, which cleaves lipoprotein receptor-related protein 6 to trigger aging-associated Wnt receptor signaling. C1q binds to apoptotic cells and the activated C1 proteases cleave nuclear antigens. C1s also cleaves MHC class I molecule and potentially numerous other proteins. The diversity of C1q ligands and C1 protease substrates renders C1 complex versatile and modular so that it can adapt to multiple molecular and cellular processes besides the complement system.
Keywords
- C1q
- aging
- autoimmunity
- complement C1
- dendritic cell
- infection
- inflammation
- macrophage
The global spinal sagittal alignment varies widely among healthy individuals as it is affected by not only race, but also aging. We investigated age-related changes in the spinal alignment in asymptomatic Japanese individuals. The subjects comprised 220 individuals without any spine-related neurological symptoms or treatment history thereof who visited our outpatient clinic. Lateral radiographs of the whole spine were taken for all subjects in the standing position. Based on the images obtained, spino-pelvic parameters were calculated using Jackson's method so as to analyze any correlations with age. TIA, TK, and C2-C7A were found to markedly increase with age from late middle age (P < 0.05). No correlation with aging was found for lumbosacral parameters or sagittal balance (P > 0.05). However, there were 22 subjects (10%) with C7SVA > 50 mm, with those aged 70 years or older accounting for half of this subpopulation. Sagittal balance tended to be retained even in elderly subjects if lumbosacral lordosis was large enough to compensate for thoracic kyphosis. A very strong correlation was found between the L1 slope and whole-spine sagittal balance (P < 0.0001, r = -0.497). Increases in cervicothoracic curvature occurring along with thoracic deformation underlie age-related changes in the spine. In contrast, the lumbosacral spine compensates in such a manner so as to maintain the sagittal balance. The whole-spine sagittal balance can deteriorate if the compensatory changes in the lumbosacral spine are insufficient. The L1 slope is a central parameter that defines the whole-spine sagittal balance. PI; pelvic incidence; SS; sacral slope; PT; pelvic tilt; LL; lumbar lordosis; C7SVA; C7 sagittal vertical axis; SSA; spinosacral angle; TK; thoracic kyphosis; C2-C7SVA; C2-C7 sagittal vertical axis; C2-C7A; C2-C7 Angle; TIA; thoracic inlet angle; NT; neck tilt.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cervical Vertebrae
- Cohort Studies
- Female
- Humans
- Japan
- Male
- Middle Aged
- Postural Balance
- Posture
- Spinal Cord
- Spine
- Young Adult
Keywords
- Global spinal alignment
- Japanese population
- age-related variations
Previous studies have shown that the aging kidney has a marked loss of α(E)-catenin in proximal tubular epithelium. α-Catenin, a key regulator of the actin cytoskeleton, interacts with a variety of actin-binding proteins. Cisplatin-induced loss of fascin2, an actin bundling protein, was observed in cells with a stable knockdown of α(E)-catenin (C2 cells), as well as in aging (24 mon), but not young (4 mon), kidney. Fascin2 co-localized with α-catenin and the actin cytoskeleton in NRK-52E cells. Knockdown of fascin2 increased the susceptibility of tubular epithelial cells to cisplatin-induced injury. Overexpression of fascin2 in C2 cells restored actin stress fibers and attenuated the increased sensitivity of C2 cells to cisplatin-induced apoptosis. Interestingly, fascin2 overexpression attenuated cisplatin-induced mitochondrial dysfunction and oxidative stress in C2 cells. These data demonstrate that fascin2, a putative target of α(E)-catenin, may play important role in preventing cisplatin-induced acute kidney injury.
MeSH Terms
- Aging
- Animals
- Antineoplastic Agents
- Apoptosis
- Carrier Proteins
- Catenins
- Cell Line
- Cisplatin
- Gene Expression Regulation
- Kidney
- Microfilament Proteins
- Protein Transport
- Rats
Keywords
- Actin
- Aging
- Apoptosis
- Fascin2
- Mitochondria
- α-Catenin
To analyze characteristics of type II odontoid fracture (TII-OF), including clinical and radiographic factors, that influence surgical planning in 8 Latin American centers. Retrospective chart review was performed of 88 patients with TII-OF between 2004 and 2015 from 8 Latin American centers. Parameters studied included 1) demographic data and causes of TII-OF, 2) clinical and neurologic presentation, 3) characteristics of fracture (degree of odontoid displacement, displacement of odontoid relative to C2 body, anatomy of fracture line, distance between fragments, presence of comminution, contact area between odontoid and C2 body), 4) type of treatment, and 5) clinical and radiographic outcome. Bone fusion was assessed using computed tomography. Mean patient age was 45.33 years ± 23.54; 78.4% of patients were male. Surgery was the primary treatment in 65 patients (73.8%), with an anterior approach in 64.6%. Surgery was usually preferred in patients with posterior or horizontal oblique fracture lines, local pain, and a smaller bone contact surface between the odontoid and the body of C2. A posterior approach was chosen when distance between the fractured bone fragments was >2 mm or after failed conservative or anterior odontoid screw treatment in a symptomatic patient. The treatment of choice for TII-OF in 8 Latin American trauma centers was surgery through an anterior approach using screw fixation. Posterior segmental C1-C2 fixation was indicated when distance between bone fragments was >2 mm and in symptomatic patients with nonunion.
MeSH Terms
- Accidental Falls
- Accidents, Traffic
- Athletic Injuries
- Bone Screws
- Braces
- Female
- Fracture Fixation
- Humans
- Latin America
- Male
- Middle Aged
- Odontoid Process
- Postoperative Complications
- Radiography
- Retrospective Studies
- Spinal Fractures
- Surgicenters
- Treatment Outcome
Keywords
- Conservative treatment
- Geriatrics
- Latin America
- Surgical procedures
- Type II odontoid fracture
This investigation examined differences in functional sit-to-stand power/velocity between cohorts of adults aged 18-97 years. This study included 264 healthy adults classified into four cohorts (18-40, C1; 60-69, C2; 70-79, C2; ≥ 80, C4). Participants completed the sit-to-stand task five times. Power and velocity were measured via the TENDO power analyzer. Absolute average power was maintained from C1-C3, but decreased (p < .01) in C4. Absolute peak power decreased between C1-C2 (p < .01), was similar between C2-C3, and decreased in C4 (p < .01). Relative (to body weight) average and peak power decreased between C1-C2 (p < .01), was similar between C2-C3, and decreased in C4 (p < .01). Average velocity was similar between C1 and C2, but decreased in C3 (p < .01) and C4 (p < .01), respectively. Peak velocity was significantly different between all cohorts (p < .01). Declines in functional power may plateau during the seventh and eighth decades, accelerating after 80 years.
MeSH Terms
- Activities of Daily Living
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cross-Sectional Studies
- Female
- Humans
- Lower Extremity
- Male
- Middle Aged
- Muscle Strength
- Muscle, Skeletal
- Physical Fitness
Keywords
- activities of daily living
- aging
- functional fitness
- lower-body power
- older adult
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
We sought to evaluate the long-term C1-C2 fusion rates, fracture healing, and functional outcomes in geriatric patients with type II odontoid fracture treated with posterior fixation with polyaxial C1 lateral mass screws and C2 pars screws. Twenty-one consecutive patients between 2005 and 2011 with Anderson and D'Alonzo type II odontoid fracture underwent a posterior atlantoaxial fixation with polyaxial C1 lateral mass screws and C2 pars screws. A long-term clinical and radiologic follow-up was achieved in all patients with a mean follow-up period of 53.28 ± 15.41 months (range 38-91 months). All 21 patients had bilateral C1 lateral mass screws and bilateral C2 pars screws. Correct positioning of the C1 lateral mass screws and C2 pars screws was observed in all 42 placements by postoperative computed tomography scans. No vascular or neurologic complication was noted. At the last follow-up, 20 patients (95.24%) had a solid fusion (defined as Lenke fusion grade A or B) while 1 patient (4.76%) had a partial fusion (Lenke fusion grade C). Overall, no hardware failures occurred in any patient. Odontoid fracture healing was achieved in 18 patients out of 21 (85.71%). The mean postoperative Neck Disability Index score was 12.73%, and neck motion was within normal physiologic limits at 12 months. This study adds to the evidence that posterior atlantoaxial fixation with polyaxial C1 lateral mass screws and C2 pars screws is a safe and effective surgical option in the treatment of odontoid fractures including long-term stability.
MeSH Terms
- Aged
- Aged, 80 and over
- Atlanto-Axial Joint
- Bone Screws
- Cohort Studies
- Female
- Geriatrics
- Humans
- Male
- Odontoid Process
- Spinal Fractures
- Spinal Fusion
- Tomography, X-Ray Computed
- Treatment Outcome
Keywords
- Elderly
- Pars screws
- Posterior C1-C2 fixation
- Type II odontoid fractures
This study aimed (1) to assess the influence of age, sex, blood glucose, and body mass index on the F fluoro-deoxy-glucose (F-FDG) uptake in normal spinal cord; (2) to quantitatively evaluate contamination of the spinal cord SUVmax by the adjacent vertebral marrow activity; and (3) to investigate the validity of normalizing spinal cord SUVmax against lumbar thecal sac SUVmax. Two hundred positron emission tomography-computed tomography examinations of subjects with normal spinal cord were retrospectively reviewed. SUVmax of spinal cord and vertebral body was obtained at C2, C5, T6, T12, and L3 levels. Pearson correlation coefficients (r) were obtained at each level between spinal cord SUVmax and vertebral marrow SUVmax, age, body mass index, and blood glucose. Cord to background ratio (CTB) was calculated as the ratio between SUVmax of spinal cord and SUVmax of L3 thecal sac. The coefficient of variation (CV) of spinal cord SUVmax was compared with the CV of CTB. Spinal cord SUVmax was highest at C2 (mean, 1.76) and lowest at T6 (mean, 1.37) with SD of 0.32 to 0.36 SUV. Sex (P > 0.45), age (r: -0.25 to -0.06), body mass index (r: 0.19 to 0.27), and blood glucose (r: -0.17 to 0.22) had no impact on the spinal cord SUVmax. A moderate to strong positive correlation (r: 0.66-0.80) was found between spinal cord SUVmax and the corresponding vertebral marrow SUVmax. The CV of CTB was greater (0.28-0.32) than the CV of spinal cord SUVmax (0.19-0.25) across all levels. Of the variables studied, only contamination from adjacent vertebral marrow activity significantly affected the SUVmax of spinal cord. This contamination should be corrected for when reporting spinal cord FDG uptake. Lumbar thecal sac is not a valid reference for normalizing spinal cord FDG uptake.
MeSH Terms
- Age Distribution
- Aging
- Bone Marrow
- Cohort Studies
- Dura Mater
- Female
- Florida
- Fluorodeoxyglucose F18
- Humans
- Image Interpretation, Computer-Assisted
- Lumbar Vertebrae
- Male
- Middle Aged
- Positron-Emission Tomography
- Radiopharmaceuticals
- Reference Values
- Reproducibility of Results
- Sensitivity and Specificity
- Sex Distribution
- Spinal Cord
Standard-of-care chemo- or radio-therapy can induce, besides tumor cell death, also tumor cell senescence. While senescence is considered to be a principal barrier against tumorigenesis, senescent cells can survive in the organism for protracted periods of time and they can promote tumor development. Based on this emerging concept, we hypothesized that elimination of such potentially cancer-promoting senescent cells could offer a therapeutic benefit. To assess this possibility, here we first show that tumor growth of proliferating mouse TC-1 HPV-16-associated cancer cells in syngeneic mice becomes accelerated by co-administration of TC-1 or TRAMP-C2 prostate cancer cells made senescent by pre-treatment with the anti-cancer drug docetaxel, or lethally irradiated. Phenotypic analyses of tumor-explanted cells indicated that the observed acceleration of tumor growth was attributable to a protumorigenic environment created by the co-injected senescent and proliferating cancer cells rather than to escape of the docetaxel-treated cells from senescence. Notably, accelerated tumor growth was effectively inhibited by cell immunotherapy using irradiated TC-1 cells engineered to produce interleukin IL-12. Collectively, our data document that immunotherapy, such as the IL-12 treatment, can provide an effective strategy for elimination of the detrimental effects caused by bystander senescent tumor cells in vivo.
MeSH Terms
- Animals
- Antineoplastic Agents
- Bystander Effect
- Cell Line, Tumor
- Cellular Senescence
- Combined Modality Therapy
- Cytokines
- Docetaxel
- Immunotherapy, Adoptive
- Interleukin-12
- Male
- Mice, Inbred C57BL
- Neoplasms, Experimental
- Taxoids
- Time Factors
- Tumor Burden
Keywords
- IL-12
- cancer chemotherapy
- cell therapy
- cellular senescence
- docetaxel
Age-related macular degeneration (AMD) affects the macula and is the leading cause of significant and irreversible central visual loss. It is the most common cause of visual loss in people aged more than 60 years. This disease affects 2.5 million individuals in Europe. AMD is caused by both environmental and genetic factors. Numerous risk factors have been reported, but the pathogenesis of AMD is complex and fairly understood. Age, female gender, obesity, race, education status, family history, hyperopia, iris color, cigarette smoking, previous cataract surgery, history of cardiovascular and cerebrovascular disease, diabetes, sunlight exposure and many other factors have been shown to be associated with AMD development. Scientific evidence shows that genes may play a role in the development of nearly 3 out of 4 cases of this devastating eye disease. The genes that have been shown to be associated with AMD are genes encoding complement system components such as CFH, C2, C3, CFB, and other.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Diabetes Complications
- Europe
- Female
- Genetic Predisposition to Disease
- Humans
- Macular Degeneration
- Male
- Middle Aged
- Obesity
- Prevalence
- Risk Factors
Keywords
- Early and late age-related macular degeneration
- Genes
- Risk factors
Considering the biological function of α-tocopherol (α-Toc) as a potent protective factor against oxidative stress, this antioxidant is in the focus of aging research. To understand the role of α-Toc during aging we investigated α-Toc concentrations in young and aged primary human fibroblasts after supplementation with RRR-α-Toc. Additionally, α-Toc contents were determined in brain, kidney, and liver tissue of 10 week-, 18 month-, and 24 month-old mice, which were fed a standard diet containing 100 mg/kg dl-α-tocopheryl acetate. α-Toc concentrations in isolated lysosomes and the expression of the α-Toc transport proteins Niemann Pick C1 (NPC1), Niemann Pick C2 (NPC2), and lipoprotein lipase were also analyzed. Obtained data show a significant age-related increase of α-Toc in murine liver, kidney, and brain tissue as well as in human dermal fibroblasts. Also liver and kidney lysosomes are marked by elevated α-Toc contents with aging. NPC1 and NPC2 protein amounts are significantly decreased in adult and aged murine kidney tissue. Also aged human dermal fibroblasts show decreased NPC1 amounts. Supplementation of young and aged fibroblasts led also to decreased NPC1 amounts, suggesting a direct role of this protein in α-Toc distribution. Our results indicate an age-dependent increase of α-Toc in different murine tissues as well as in human fibroblasts. Furthermore saturation and intracellular distribution of α-Toc seem to be strongly dependent on the availability of this vitamin as well as on the presence of the lysosomal protein NPC1. © 2016 BioFactors, 42(3):307-315, 2016.
MeSH Terms
- Adult
- Aging
- Animals
- Antioxidants
- Brain
- Carrier Proteins
- Fibroblasts
- Gene Expression Regulation
- Glycoproteins
- Humans
- Intracellular Signaling Peptides and Proteins
- Kidney
- Lipoprotein Lipase
- Liver
- Lysosomes
- Male
- Membrane Glycoproteins
- Mice
- Oxidative Stress
- Vesicular Transport Proteins
- alpha-Tocopherol
Keywords
- aging
- lipid peroxidation
- lysosomes
- oxidative stress
- α-tocopherol
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
{{medline-entry |title=Tract-specific and age-related variations of the spinal cord microstructure: a multi-parametric MRI study using diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT). |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27100385 |abstract=Being able to finely characterize the spinal cord (SC) microstructure and its alterations is a key point when investigating neural damage mechanisms encountered in different central nervous system (CNS) pathologies, such as multiple sclerosis, amyotrophic lateral sclerosis or myelopathy. Based on novel methods, including inhomogeneous magnetization transfer (ihMT) and dedicated SC probabilistic atlas post-processing, the present study focuses on the in vivo characterization of the healthy SC tissue in terms of regional microstructure differences between (i) upper and lower cervical vertebral levels and (ii) sensory and motor tracts, as well as differences attributed to normal aging. Forty-eight healthy volunteers aged from 20 to 70 years old were included in the study and scanned at 3 T using axial high-resolution T2 *-w imaging, diffusion tensor imaging (DTI) and ihMT, at two vertebral levels (C2 and C5). A processing pipeline with minimal user intervention, SC segmentation and spatial normalization into a reference space was implemented in order to assess quantitative morphological and structural parameters (cross-sectional areas, scalar DTI and MT/ihMT metrics) in specific white and gray matter regions of interest. The multi-parametric MRI metrics collected allowed upper and lower cervical levels to be distinguished, with higher ihMT ratio (ihMTR), higher axial diffusivity (λ∥ ) and lower radial diffusivity (λ⊥ ) at C2 compared with C5. Significant differences were also observed between white matter fascicles, with higher ihMTR and lower λ∥ in motor tracts compared with posterior sensory tracts. Finally, aging was found to be associated with significant metric alterations (decreased ihMTR and λ∥ ). The methodology proposed here, which can be easily transferred to the clinic, provides new insights for SC characterization. It bears great potential to study focal and diffuse SC damage in neurodegenerative and demyelinating diseases. Copyright © 2016 John Wiley