Age-related Expression Patterns Research Articles

Aging affects the mouse brain in a region-specific manner.

Aging-related cognitive decline is emerging as a health concern during the aging process of the global population. Hahn and colleagues found that glial aging was particularly accelerated in white matter compared to cortical regions. Specialized neuronal populations showed region-specific changes in gene expression. Acute dietary restriction triggers a reprogramming of genes associated with the circadian clock in glial cells, whereas injections of young mouse plasma selectively reverse age-related expression patterns. The discovery of region-specific aging could enhance our understanding of the aging process and offer new possibilities for innovative treatment strategies and interventions for cognitive impairments related to aging.

Exploring ocular fibulin-3 (EFEMP1): Anatomical, age-related, and species perspectives

Fibulin-3 (FBLN3, aka EFEMP1) is a secreted extracellular matrix (ECM) glycoprotein implicated in ocular diseases including glaucoma and age-related macular degeneration. Yet surprisingly, little is known about its native biology, expression patterns, and localization in the eye. To overcome these shortcomings, we conducted gene expression analysis and immunohistochemistry for FBLN3 in ocular tissues from mice, pigs, non-human primates, and humans. Moreover, we evaluated age-related changes in FBLN3 and FBLN3-related ECM remodeling enzymes/inhibitors in aging mice. We found that FBLN3 displayed distinct staining patterns consistent across the mouse retina, particularly in the ganglion cell layer and inner nuclear layer (INL). In contrast, human retinas exhibited a unique staining pattern, with enrichment of FBLN3 in the retinal pigment epithelium (RPE), INL, and outer nuclear layer (ONL) in the peripheral retina. This staining transitioned to the outer plexiform layer (OPL) in the central retina/macula, and was accompanied by reduced RPE immunoreactivity approaching the fovea. Surprisingly, we found significant age-related increases in FBLN3 expression and protein abundance in the mouse retina which was paralleled by reduced transcript levels of FBLN3-degrading enzymes (i.e., Mmp2 and Htra1). Our findings highlight important species-dependent, retinal region-specific, and age-related expression and localization patterns of FBLN3 which favor its accumulation during aging. These findings contribute to a better understanding of FBLN3's role in ocular pathology and provide valuable insights for future FBLN3 research.

Melatonin and Sirtuins in Buccal Epithelium: Potential Biomarkers of Aging and Age-Related Pathologies.

Melatonin (MT) and sirtuins (SIRT) are geroprotective molecules that hold back the aging process and the development of age-related diseases, including cardiovascular pathologies. Buccal epithelium (BE) sampling is a non-invasive procedure, yielding highly informative material for evaluating the expression of genes and proteins as well as the synthesis of molecules. Among these, MT and SIRTs are valuable markers of the aging process and age-related pathologies. The purpose of this study was to examine age-related expression patterns of these signaling molecules, in particular MT, SIRT1, SIRT3, and SIRT6 in BE of subjects of different ages with and without arterial hypertension (AH). We used real-time polymerase chain reaction (RT-PCR) and immunofluorescence analysis by confocal microscopy. We found that MT immunofluorescence intensity in BE decreases with aging, more evidently in AH patients. SIRT3 and SIRT6 genes expression and immunofluorescence intensity in BE was decreased in aging controls. In AH patients, SIRT1, SIRT3, and SIRT6 gene expression and immunofluorescence intensity in BE was decreased in relation to age and in comparison with age-matched controls. In conclusion, the evaluation of MT and sirtuins in BE could provide a non-invasive method for appraising the aging process, also when accompanied by AH.

Up-Regulation of SorCS1, an Important Sorting Receptor, in the Retina of a Form-Deprivation Rat Model.

Visually guided regulation is a sophisticated and active process, whereby sensory input helps to shape ocular development. Here, we sought to investigate the potential involvement of SorCS1, an important protein in synaptic transmission in neuron, in retinal development. A form-deprivation (FD) rat model was established. Ocular variations induced by FD were examined, including changes to eye axial length and retinal thickness. Scotopic electroretinogram (ERG) was used to examine retinal function. RD-PCR assays were screened for differentially expressed genes in FD rat eyes. Immunofluorescence staining identified the expression pattern and localization of SorCS1 in rat retina, with or without FD treatment. Additionally, primary retinal neural cells were cultured and incubated with or without a light-dark cycle, and western blot and real-time PCR assays were used to examine the expression of SorCS1. Retinal neural cells were treated with recombinant SorCS1 (h-SorCS1) coated with beads in serum-free conditions to test for effects on cellular physiology and expression of neurotransmitters involved in visual development. To monitor cell viability, a CCK8 assay was employed. Our data demonstratedthat FD led to ocular axial elongation and retinal thinning. ERG tests showed FD impaired electrophysiological function in rat. An age-related expression pattern of SorCS1 was observed in the rat retina, and SorCS1 was significantly up-regulated in the FD rat retina. In addition, in vitro evidence suggested a strong correlation between light exposure and SorCS1 expression. Furthermore, treatment of retinal neural cells with h-SorCS1-beads promoted cell viability, neurite outgrowth, and up-regulation of inhibitory neurotransmitter expression, which implies that over-expression of SorCS1 may cause abnormal retinal development. Our findings suggest that SorCS1 is involved in the physiological processes of light/visually guided ocular growth.

Longitudinal comparative transcriptomics reveals unique mechanisms underlying extended healthspan in bats.

Bats are the longest-lived mammals, given their body size. However, the underlying molecular mechanisms of their extended healthspans are poorly understood. To address this question we carried out an eight-year longitudinal study of ageing in long-lived bats (Myotis myotis). We deep-sequenced ~1.7 trillion base pairs of RNA from 150 blood samples collected from known aged bats to ascertain the age-related transcriptomic shifts and potential microRNA-directed regulation that occurred. We also compared ageing transcriptomic profiles between bats and other mammals by analysis of 298 longitudinal RNA sequencing datasets. Bats did not show the same transcriptomic changes with age as commonly observed in humans and other mammals, but rather exhibited a unique, age-related gene expression pattern associated with DNA repair, autophagy, immunity and tumour suppression that may drive their extended healthspans. We show that bats have naturally evolved transcriptomic signatures that are known to extend lifespan in model organisms, and identify novel genes not yet implicated in healthy ageing. We further show that bats' longevity profiles are partially regulated by microRNA, thus providing novel regulatory targets and pathways for future ageing intervention studies. These results further disentangle the ageing process by highlighting which ageing pathways contribute most to healthy ageing in mammals.

Age-related deregulation of TDP-43 after stroke enhances NF-\u03baB-mediated inflammation and neuronal damage

BackgroundTDP-43 has been identified as a disease-associated protein in several chronic neurodegenerative disorders and increasing evidence suggests its potentially pathogenic role following brain injuries. Normally expressed in nucleus, under pathological conditions TDP-43 forms cytoplasmic ubiquitinated inclusions in which it is abnormally phosphorylated and cleaved to generate a 35 and a 25 kDa C-terminal fragments. In the present study, we investigated age-related expression patterns of TDP-43 in neurons and glia and its role as modulator of inflammation following ischemic injury.MethodsWild-type and TDP-43 transgenic mice of different age groups were subjected to transient middle cerebral artery occlusion. The role of TDP-43 in modulation of inflammation was assessed using immunofluorescence, Western blot analysis, and in vivo bioluminescence imaging. Finally, post-mortem stroke human brain sections were analyzed for TDP-43 protein by immunohistochemistry.ResultsWe report here an age-related increase and formation of ubiquitinated TDP-43 cytoplasmic inclusions after stroke. The observed deregulation in TDP-43 expression patterns was associated with an increase in microglial activation and innate immune signaling as revealed by in vivo bioluminescence imaging and immunofluorescence analysis. The presence of ubiquitinated TDP-43 aggregates and its cleaved TDP-35 and TDP-25 fragments was markedly increased in older, 12-month-old mice leading to larger infarctions and a significant increase in in neuronal death. Importantly, unlike the hallmark neuropathological features associated with chronic neurodegenerative disorders, the TDP-43-positive cytoplasmic inclusions detected after stroke were not phosphorylated. Next, we showed that an increase and/or overexpression of the cytoplasmic TDP-43 drives the pathogenic NF-κB response and further increases levels of pro-inflammatory markers and ischemic injury after stroke in age-dependent manner. Finally, analyses of the post-mortem stroke brain tissues revealed the presence of the cytoplasmic TDP-43 immunoreactive structures after human stroke.ConclusionTogether, our findings suggest that the level of cytoplasmic TDP-43 increases with aging and may act as an age-related mediator of inflammation and neuronal injury after stroke. Thus, targeting cytoplasmic TDP-43 may have a therapeutic potential after stroke.

Altered gene expression pattern indicates the differential regulation of the immune response system as an important factor in cardiac aging.

Numerous changes occur in the old myocardium which finally cause lower cardiac output and, therefore, circulatory dysfunction. In order to identify an age-related gene expression pattern, we analyzed left ventricular myocardium of adult (6 months) and old (24 months) mice by use of whole genome expression arrays. About 2.3% of genes expressed above the median value of all genes were differentially expressed in old hearts. Nearly all of them were upregulated. After application of defined exclusion criteria, 98 genes were selected for a more detailed analysis. About one third of the 98 genes codes for factors involved in the immune reaction, such as chemokines (CCLs 6, 8, 9), proteins of the S100 family (S100s 4, 8, 9, 10, 11), complement components (C1qa, C1qb, C1qc, C3, C4b), bacteria/virus-induced genes (lysozyme 1/2, interferon-activated genes), and pro-inflammatory caspases (Casp1, Casp4, Casp12). Predominantly, genes coding for factors of the immune reaction were simultaneously upregulated in the kidneys and lungs of old mice, thereby emphasizing the pivotal role of immune cells in tissue aging. In conclusion, myocardial aging is mainly associated with an altered expression pattern of molecules involved in the immune reaction.

Effect of advanced age on plasma homocysteine levels and its association with ischemic stroke in non-valvular atrial fibrillation.

BackgroundElevated homocysteine (Hcy) has been reported to be associated with cardiovascular events in atrial fibrillation (AF) patients, while the age-related expression pattern of plasma Hcy in AF remains unknown. The study was aimed to investigate the effect of advanced age on plasma Hcy levels and its association with ischemic stroke in non-valvular AF patients.MethodsA total of 2562 consecutive patients with non-valvular AF and 535 controls were enrolled and divided into six age groups. Plasma Hcy levels were analyzed among different age groups, and the effect of advanced age on Hcy was investigated.ResultsPlasma Hcy levels did not show any difference among groups aged below 65 years, while it increased sharply in patients aged 65–74 years and aged over 75 years (15.7 ± 4.6 µmol/L, 17.1 ± 4.9 µmol/L, both P < 0.01 compared with the first four age groups). Hcy was much higher in AF patients than in controls at the same age group (all P < 0.05). The proportion of patients with hyperhomocysteinemia increased gradually with age from 32.3%, 29.2%, 31.2%, 32.4%, 45.9%, to 51.4% in six age groups. The concentration of Hcy in AF patients with ischemic stroke increased progressively with age, and was higher than those without stroke at the same age. Logistic regression analysis demonstrated that age 65–74 years [odds ratios (OR): 1.742, 95% confidence interval (CI): 1.223–2.482, P = 0.002] and age ≥ 75 years (OR: 2.637, 95% CI: 1.605–4.335, P < 0.001) were significantly independent predictors of elevated plasma Hcy levels.ConclusionsAdvanced age was significantly associated with elevated Hcy levels, which may provide a possible explanation for the progressive increase in ischemic stroke especially in elderly AF patients.

Genetic variation and gene expression across multiple tissues and developmental stages in a nonhuman primate.

By analyzing multi-tissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalogue of expression quantitative trait loci (eQTLs) in a non-human primate model. This catalogue contains more genome-wide significant eQTLs, per sample, than comparable human resources, and reveals sex and age-related expression patterns. Findings include a master regulatory locus that likely plays a role in immune function, and a locus regulating hippocampal long non-coding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral phenotypes relevant to neuropsychiatric disorders.

Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system

Individual age estimation has the potential to provide key information that could enhance and extend DNA intelligence tools. Following predictive tests for externally visible characteristics developed in recent years, prediction of age could guide police investigations and improve the assessment of age-related phenotype expression patterns such as hair colour changes and early onset of male pattern baldness. DNA methylation at CpG positions has emerged as the most promising DNA tests to ascertain the individual age of the donor of a biological contact trace. Although different methodologies are available to detect DNA methylation, EpiTYPER technology (Agena Bioscience, formerly Sequenom) provides useful characteristics that can be applied as a discovery tool in localized regions of the genome. In our study, a total of twenty-two candidate genomic regions, selected from the assessment of publically available data from the Illumina HumanMethylation 450 BeadChip, had a total of 177 CpG sites with informative methylation patterns that were subsequently investigated in detail. From the methylation analyses made, a novel age prediction model based on a multivariate quantile regression analysis was built using the seven highest age-correlated loci of ELOVL2, ASPA, PDE4C, FHL2, CCDC102B, C1orf132 and chr16:85395429. The detected methylation levels in these loci provide a median absolute age prediction error of ±3.07years and a percentage of prediction error relative to the age of 6.3%. We report the predictive performance of the developed model using cross validation of a carefully age-graded training set of 725 European individuals and a test set of 52 monozygotic twin pairs. The multivariate quantile regression age predictor, using the CpG sites selected in this study, has been placed in the open-access Snipper forensic classification website.

Specific Regional and Age-Related Small Noncoding RNA Expression Patterns Within Superior Temporal Gyrus of Typical Human Brains Are Less Distinct in Autism Brains

Small noncoding RNAs play a critical role in regulating messenger RNA throughout brain development and when altered could have profound effects leading to disorders such as autism spectrum disorders (ASD). We assessed small noncoding RNAs, including microRNA and small nucleolar RNA, in superior temporal sulcus association cortex and primary auditory cortex in typical and ASD brains from early childhood to adulthood. Typical small noncoding RNA expression profiles were less distinct in ASD, both between regions and changes with age. Typical micro-RNA coexpression associations were absent in ASD brains. miR-132, miR-103, and miR-320 micro-RNAs were dysregulated in ASD and have previously been associated with autism spectrum disorders. These diminished region- and age-related micro-RNA expression profiles are in line with previously reported findings of attenuated messenger RNA and long noncoding RNA in ASD brain. This study demonstrates alterations in superior temporal sulcus in ASD, a region implicated in social impairment, and is the first to demonstrate molecular alterations in the primary auditory cortex.

Age-related expression analysis of mouse liver nuclear protein binding to 3'-untranslated region of Period2 gene.

In mammals, both circadian rhythm and aging play important roles in regulating time-dependent homeostasis. We previously discovered an age-related increase element binding protein, hnRNP A3, which binds to the 3'-untranslated region (UTR) of blood coagulation factor IX (FIX). Here, we describe other members of this protein family, hnRNP C and hnRNP H, which bind to the 3'-UTR of the mouse circadian clock gene Period 2 (mPer2). RNA electrophoretic mobility shift assays using a (32)P-labeled Per2 RNA probe coupled with two-dimensional gel electrophoresis followed by MALDI-TOF/MS peptide mass fingerprint analysis was used to analyze these proteins. Western blotting suggested that the total expression of these proteins in mouse liver cell nuclei does not increase with age. Two-dimensional gel electrophoresis analysis of age-related protein expression showed that many isoforms of these proteins exist in the liver and that each protein exhibits a complex age-related expression pattern. These results suggest that many isoforms of proteins are regulated by different aging systems and that many age regulation systems function in the liver.

Profiling age-related epigenetic markers of stomach adenocarcinoma in young and old subjects.

The purpose of our study is to identify epigenetic markers that are differently expressed in the stomach adenocarcinoma (STAD) condition. Based on data from The Cancer Genome Atlas (TCGA), we were able to detect an age-related difference in methylation patterns and changes in gene and miRNA expression levels in young (n = 14) and old (n = 70) STAD subjects. Our analysis identified 323 upregulated and 653 downregulated genes in old STAD subjects. We also found 76 miRNAs with age-related expression patterns and 113 differentially methylated genes (DMGs), respectively. Our further analysis revealed that significant upregulated genes (n = 35) were assigned to the cell cycle, while the muscle system process (n = 27) and cell adhesion-related genes (n = 57) were downregulated. In addition, by comparing gene and miRNA expression with methylation change, we identified that three upregulated genes (ELF3, IL1β, and MMP13) known to be involved in inflammatory responses and cell growth were significantly hypomethylated in the promoter region. We further detected target candidates for age-related, downregulated miRNAs (hsa-mir-124–3, hsa-mir-204, and hsa-mir-125b-2) in old STAD subjects. This is the first report of the results from a study exploring age-related epigenetic biomarkers of STAD using high-throughput data and provides evidence for a complex clinicopathological condition expressed by the age-related STAD progression.

Age-dependent clinical prognostic value of histone modifications in colorectal cancer

Aging is one of the prime risk factors for the development of cancer. Expression patterns of epigenetic regulators, including histone modification levels, are altered during aging of normal cells, a phenomenon referred to as epigenetic drift. Furthermore, it is known that epigenetic mechanisms are involved in the development of cancer. We hypothesized that expression of histone modifications, acetylation of histone 3 lysine 9 (H3K9Ac) and trimethylation of histone 3 lysine 27 (H3K27me3), with reported normal age-related expression patterns might show an age-dependent prognostic value in colorectal cancer (CRC). To quantify expression, we performed immunohistochemical staining of these histone modifications on a tissue microarray containing colorectal tissues of the 254 patients with TNM stage I-III CRC. Stratification of patients according to survival status revealed age-related tumor expression patterns of both H3K9Ac and H3K27me3. Decreased expression with advancing age was observed in patients who were alive after follow-up (no-event group), whereas increased expression with advancing age was observed in patients who presented with a recurrence or death in follow-up (event group). These opposite expression patterns translated into an age-dependent prognostic value in CRC for the individual histone modifications and their combination. The prognostic value reverses with advancing age, high nuclear expression associated with good clinical outcome in young adults, and, in contrast, with worse clinical outcome in elderly patients. In conclusion, for the first time, we demonstrated prognostic impact of epigenetic biomarkers that reverses with advancing age. This new insight supports the hypothesis that CRC biology is different in young vs elderly patients and emphasizes the importance of focusing on age-related effects in CRC.

Characterization of the expression profile of CRBP1 and CRBP3 gene in chicken.

In this study, we quantified the expression of CRBP1 and CRBP3 in Roman layer (R) and Erlang mountainous chickens (SD02 and SD03), to discern the tissue, breed and age-related expression patterns in order to discover potential involvement in egg production and other related reproduction traits. Real-time quantitative PCR assays were developed for accurate measurement of CRBP1 and CRBP3 mRNA levels in different tissues from chickens at four ages (12, 20, 32 and 45 weeks). We found that the CRBP1 and CRBP3 were expressed in all six tissues examined in all three breeds of chicken at 32 weeks. CRBP1 mRNA levels in SD02 kidneys were slightly higher than those in SD03 and R at 12 weeks, whereas, at the other three time points, the expression levels of CRBP1 in SD03 were higher than those in SD02 and R. In addition, there was higher hepatic expression of CRBP3 mRNA in layers (R) compared to broilers (SD02 and SD03) at 20 and 32 weeks. An age-related expression pattern of CRBP1 gene was evident in liver (P < 0.01), but not in pituitary (P > 0.05). Overall, the expression level of CRBP1 gene in kidney, ovary and oviduct at the different ages had a "decline-rise-decline" trend in all three breeds. In contrast, in pituitary, hypothalamus, liver and kidney CRBP3 mRNA expression levels were significantly different at various ages (P < 0.05) and exhibited a "rise-decline-rise" pattern in all three breeds. Our results show that the expression of CRBP1 and CRBP3 in chicken tissues exhibit specific developmental changes and age-related patterns.

Highlights of This Issue

Overall breast cancer risk increases steadily beginning at about 30 years of age. To better understand the age-related gene expression changes in breast cancer, Pirone and colleagues used microarrays to characterize age-related gene expression patterns in normal breast tissue. The authors report significant associations between gene expression levels and age for over 800 probes. This study reveals breast cancer insights uncovered through the evaluation of normal breast tissue.Mean sojourn time (MST) measures the preclinical screen-detectable phase and represents how well a test can detect asymptomatic disease. For colorectal cancer screening tests, available MST estimates are associated with the older Hemoccult II tests. In this study, Zheng and Rutter present MST estimates for the newer Hemoccult SENSA tests. Using the newer tests, the authors found differences in MST relative to the location of the cancer in the colorectum. These results provide important information about the performance of Hemoccult SENSA tests as well as clues about colorectal cancer detection.A recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). To further investigate the rs865686–breast cancer association, Warren and colleagues conducted a replication study within the Breast Cancer Association Consortium. This study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk. In addition, the authors report that the strength of the breast cancer association decreased with increasing age at diagnosis.Non-Hodgkin lymphoma is a malignancy of lymphocytes, and increasing evidence points to a role for genetic variation in immune genes in the non-Hodgkin lymphoma etiology. Cerhan and colleagues conducted a 2-stage analysis of single-nucleotide polymorphisms (SNP) from 1,253 genes using an immune and inflammation gene panel. The authors report that the TAP2 coding SNP rs241447 was strongly associated with follicular lymphoma and diffuse large B-cell lymphoma but not with chronic lymphocytic leukemia. In addition, higher TAP2 expression was associated with the risk allele in both follicular lymphoma and diffuse large B-cell lymphoma tumors. These results indicate that genetic variation in antigen presentation of HLA class I molecules may play a role in lymphomagenesis.

Epigenetic regulation of developmental expression of Cyp2d genes in mouse liver

CYP2D6 expression in liver is age-dependent. Because epigenetic mechanisms, such as DNA methylation and histone modifications, modulate age-related gene expression during development, and are highly conserved among species, the current study examined the epigenetic regulation of age-related expression of the Cyp2d genes in mouse liver. DNA methylation (DNAme), histone 3 lysine 4 dimethylation (H3K4me2), and histone 3 lysine 27 trimethylation (H3K27me3) was established by ChIP-on-chip tiling microarrays from mouse livers at prenatal, neonatal, and adult stages. Levels of DNAme, H3K4me2, and H3K27me3 were analyzed in a genomic region containing the Cyp2d clustering genes and their surrounding genes. Gradually increased expression levels of the Cyp2d9, Cyp2d10, Cyp2d22, and Cyp2d26 genes from prenatal, through neonatal, to adult are associated with gradually increased levels of H3K4me2 in the nucleosomes associated with these genes. Gene expression patterns during liver development in several Cyp2d surrounding genes, such as Srebf2, Sept3, Ndufa6, Tcf2, Nfam1, and Cyb5r3, could be also explained by changes of DNA methylation, H3K4me2, or H3K27me3 in those genes. In conclusion, the current study demonstrates that the changes of DNA methylation and histone modifications are associated with age-related expression patterns of the Cyp2d genes and their surrounding genes in liver cells during development.

Modulation of Longevity and Tissue Homeostasis by the Drosophila PGC-1 Homolog

In mammals, the PGC-1 transcriptional coactivators are key regulators of energy metabolism, including mitochondrial biogenesis and respiration, which have been implicated in numerous pathogenic conditions, including neurodegeneration and cardiomyopathy. Here, we show that overexpression of the Drosophila PGC-1 homolog (dPGC-1/spargel) is sufficient to increase mitochondrial activity. Moreover, tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract extends life span. Long-lived flies overexpressing dPGC-1 display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homeostasis in old flies. Together, these results demonstrate that dPGC-1 can slow aging both at the level of cellular changes in an individual tissue and also at the organismal level by extending life span. Our findings point to the possibility that alterations in PGC-1 activity in high-turnover tissues, such as the intestine, may be an important determinant of longevity in mammals.

Age-related changes in human cervical, thoracal and lumbar intervertebral disc exhibit a strong intra-individual correlation

Intervertebral disc (IVD) degeneration is characterized as a multifactorial disease, in which the hereditary background is thought to be of high importance. Accordingly, one would expect all spinal levels (lumbar/cervical/thoracal) to be affected by above-average disc degeneration in genetically predisposed individuals. The aim of this study, therefore, was to analyze the amount of degenerative changes in different spine levels in humans from different ages. In detail, the presence, localization and abundance of histomorphological changes in the annulus fibrosus (AF) and nucleus pulposus (NP) in the cervical (C5/C6), thoracic (T2/T3) and lumbar (L2/L3) spine were investigated in complete autopsy IVD specimens (47 individuals) covering a complete age range (0-95 years). Results indicate that the highest degree of histo-degenerative changes were observed in the NP in all spine levels and showed an age-related expression pattern. With regard to the different spine levels, lumbar disc specimen showed significantly more degenerative changes compared to cervical and thoracic discs, whereas no statistical difference was observed between cervical and thoracic discs. In summary, highest grades of degeneration were observed in lumbar discs (especially in the NP). Intra-individual correlations between the degeneration score in the different levels showed a significant individual concordance. The intra-individual correlation of degenerative changes in all three examined spine regions further supports the notion that individual, i.e. genetic factors are strong predisposing factor for the development of age-related disc alterations.

Age-related changes in myelin morphology, electrophysiological property and myelin-associated protein expression of mouse sciatic nerves

This study investigated the morphological and functional changes in peripheral nerves during the maturation and aging process. In a mouse sciatic nerve model, electron micrographs revealed that the number of myelin sheath lamellae gradually increased from 1 week through 12 months of age, when it reached the peak value, and then remained unchanged until 18 months of age; electrophysiological examinations showed that the amplitude of compound muscle action potentials gradually increased from 1 week through 18 months of age and displayed a positive linear correlation with the number of myelin sheath lamellae. Western blot analysis exhibited the age-related expression patterns of four myelin-associated proteins, i.e., myelin-associated glycoprotein (MAG), myelin basic protein (MBP), glycoprotein P0 (P0) and peripheral myelin protein 22 (PMP22). And MAG, MBP and PMP22 showed linear negative or positive correlations with the number of myelin sheath lamellae. Our results suggest that the morphological and functional changes in peripheral nerves are closely related to each other and the myelin-associated proteins perform distinct actions on the formation, maturation, degeneration and regeneration of myelin sheaths.