Assessment of candidate ocular biomarkers of ageing in a South African adult population: relationship with chronological age and systemic biomarkers.
Ontology highlight
ABSTRACT:
SUBMITTER: Pathai S
PROVIDER: S-EPMC3710972 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:HIV-infected individuals have an increased risk of age-related morbidity despite antiretroviral treatment (ART). Several anatomic and functional ophthalmological parameters are associated with increasing chronological age. These may, therefore, potentially serve as biomarkers of ageing. We investigated associations between ocular parameters (lens density, retinal vessel calibre, corneal endothelium and retinal nerve fibre layer thickness) and two 'cellular' biomarkers of ageing (leukocyte telomere length and CDKN2A expression) and with frailty in a cross-sectional study of 216 HIV-infected individuals. All ocular parameters, telomere length and frailty were associated with chronological age, whereas CDKN2A expression was not. Retinal venular calibre and lens density were associated with shorter telomere length (p-trend=0.04, and 0.08, respectively), whereas CDKN2A expression and frailty status were not associated with ocular parameters. Longitudinal studies are warranted to assess the integration of retinal vascular calibre and lens density with systemic markers to develop an overall index of biological ageing in HIV infection.
| S-EPMC3818088 | biostudies-literature
Project description:Composition of the gut microbiota changes during ageing, but questions remain about whether age is also associated with deficits in microbiome function and whether these changes occur sharply or progressively. The ability to define these deficits in populations of different ages may help determine a chronological age threshold at which deficits occur and subsequently identify innovative dietary strategies for active and healthy ageing. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics in three well-defined age groups consisting of 30 healthy volunteers, namely, ten infants, ten adults and ten elderly individuals. Samples from each volunteer at intervals of up to 6 months (n = 83 samples) were used for validation. Ageing gradually increases the diversity of gut bacteria that actively synthesize proteins, that is by 1.4-fold from infants to elderly individuals. An analysis of functional deficits consistently identifies a relationship between tryptophan and indole metabolism and ageing (p < 2.8e-8 ). Indeed, the synthesis of proteins involved in tryptophan and indole production and the faecal concentrations of these metabolites are directly correlated (r2 > .987) and progressively decrease with age (r2 > .948). An age threshold for a 50% decrease is observed ca. 11-31 years old, and a greater than 90% reduction is observed from the ages of 34-54 years. Based on recent investigations linking tryptophan with abundance of indole and other "healthy" longevity molecules and on the results from this small cohort study, dietary interventions aimed at manipulating tryptophan deficits since a relatively "young" age of 34 and, particularly, in the elderly are recommended.
| S-EPMC6974723 | biostudies-literature
Project description:BackgroundMuscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age.ResultsMuscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu).ConclusionsThis study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.
| S-EPMC4523020 | biostudies-literature
Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease which is characterized by the presence of autoantibodies. It will be helpful if specific serum biomarkers can be used for monitoring the disease activity as well as differentiating SLE from other diseases. For this purpose, we used a label free-based two dimensional liquid chromatography mass spectrometry platform to analyze serum samples from SLE patients in active or inactivestage. Significant differences were found for 42 serum proteins implicated in pathways including complement and coagulation cascades. Further gene set enrichment analysis revealed that gene sets including formation of fibrin clot, ECM glycoproteins and innate immune system were highly correlated with the SLE disease activity. To further assess the validity of these findings, thrombospondin-4 was selected for subsequent ELISA assays. We also explored the autoantibody of three candidate biomarkers in larger cohorts including SLE, Rheumatoid arthritis, Sjogrensyndrome patients and normal controls. Our findings provided valuable information on the proteomic changes in the serum of different SLE disease activity. Serum properdin, collectin-11 and thrombospondin-4 were valuable in monitoring the disease activity of SLE, and the autoantibodies to them may be valuable in differentiating SLE from other diseases for clinical diagnosis in the future.
| S-EPMC6965801 | biostudies-literature
Project description:BACKGROUND:Advanced age is associated with cognitive and physical decline and is a major risk factor for a multitude of disorders. There is also a gap in life expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. Here, we investigate age-by-sex differences in blood-based DNA methylation in an unrelated cohort of 2586 individuals between the ages of 18 and 87?years, with replication in a further 4450 individuals between the ages of 18 and 93?years. METHODS:Linear regression models were applied, with stringent genome-wide significance thresholds (p?<?3.6?×?10-8) used in both the discovery and replication data. A second, highly conservative mixed linear model method that better controls the false-positive rate was also applied, using the same genome-wide significance thresholds. RESULTS:Using the linear regression method, 52 autosomal and 597 X-linked CpG sites, mapping to 251 unique genes, replicated with concordant effect size directions in the age-by-sex interaction analysis. The site with the greatest difference mapped to GAGE10, an X-linked gene. Here, DNA methylation levels remained stable across the male adult age range (DNA methylation by age r?=?0.02) but decreased across female adult age range (DNA methylation by age r?=?-?0.61). One site (cg23722529) with a significant age-by-sex interaction also had a quantitative trait locus (rs17321482) that is a genome-wide significant variant for prostate cancer. The mixed linear model method identified 11 CpG sites associated with the age-by-sex interaction. CONCLUSION:The majority of differences in age-associated DNA methylation trajectories between sexes are present on the X chromosome. Several of these differences occur within genes that have been implicated in sexually dimorphic traits.
| S-EPMC6938636 | biostudies-literature
Project description:Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of "sleeping sickness". Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control.
| S-EPMC5152828 | biostudies-literature
Project description:In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown.
| S-EPMC4942926 | biostudies-other
Project description:Emotions towards a relationship partner provide relevant and specific information about relationship quality. Based on this assumption the present study was performed to identify different types of emotional relationship quality of middle-aged adult children with their ageing parents. This was done by cluster analytic procedures in a sample of 1,208 middle-aged adult children (482 men, 726 women). Using ratings of positive and negative emotions towards their mother and father as grouping variables, the same four-cluster solution emerged for both the child-mother relationship and the child-father relationship. Clusters were labelled as amicable, disharmonious, detached and ambivalent relationships. Results showed that especially amicable relationships clearly prevailed followed by ambivalent, detached and disharmonious relationships. Clusters differed significantly with respect to gender of adult child, willingness to support, expected parental support and overt conflicts. In a cross-classification of cluster membership regarding the child-mother relationship (four clusters) and the child-father relationship (four clusters), all possible 16 combinations were observed, with a considerable degree of divergence regarding the type of relationship quality within the same family. Results are discussed with respect to types of emotional relationship quality, within family differences and the intrafamilial regulation of relationship quality.
| S-EPMC5547348 | biostudies-other
Project description:Systemic lupus erythematosus (SLE) is a challenging disease caused by both genetic and environmental influences. Symptoms of SLE vary and they may come and go, therefore diagnosis and treatment of the disease is difficult. Serum metabolites can not only serve as biomarkers of the disease but also can reveal the pathogenesis. Thus, it is important to find reliable biomarkers for early diagnosis and treatment of the disease, which would greatly benefit SLE patients. Our purpose was to study the metabolite profiles in active systemic lupus erythematosus and to identify metabolites that are significantly altered. Serum samples from 34 participants (17 SLE and 17 healthy) were collected and analyzed. Untargeted lipidomics and metabolomics were used to study the metabolite profiles in serum by high-performance liquid chromatography-tandem mass spectrometry. Serum enzyme-linked immunosorbent assay was performed to validate differentially expressed metabolites. We identified differential expression of over 50 metabolites. These metabolites include several new SLE related metabolite species such as ceramide, trimethylamine N-oxide, xanthine, which were significantly elevated in the serum of active systemic lupus erythematosus patients. Some other metabolites include acylcarnitine, caffeine, hydrocortisone, itaconic acid and serotonin were down-regulated. Our study characterizes the circulating metabolites in active systemic lupus erythematosus and provides several candidate biomarkers for the diagnosis and potential therapeutic targets of the disease.
| S-EPMC6945160 | biostudies-literature
Project description:BackgroundSexual activity may be less likely to occur during periods of school enrolment because of the structured and supervised environment provided, the education obtained and the safer peer networks encountered while enrolled. We examined whether school enrolment was associated with teen pregnancy in South Africa.MethodsUsing longitudinal demographic surveillance data from the rural Agincourt sub-district, we reconstructed the school enrolment status from 2000 through 2011 for 15 457 young women aged 12-18 years and linked them to the estimated conception date for each pregnancy during this time. We examined the effect of time-varying school enrolment on teen pregnancy using a Cox proportional hazard model, adjusting for: age; calendar year; household socioeconomic status; household size; and gender, educational attainment and employment of household head. A secondary analysis compared the incidence of pregnancy among school enrolees by calendar time: school term vs school holiday.ResultsSchool enrolment was associated with lower teen pregnancy rates [adjusted hazard ratio (95% confidence interval): 0.57 (0.50, 0.65)].This association was robust to potential misclassification of school enrolment. For those enrolled in school, pregnancy occurred less commonly during school term than during school holidays [incidence rate ratio (95% confidence interval): 0.90 (0.78, 1.04)].ConclusionsYoung women who drop out of school may be at higher risk for teen pregnancy and could likely benefit from receipt of accessible and high quality sexual health services. Preventive interventions designed to keep young women in school or addressing the underlying causes of dropout may also help reduce the incidence of teen pregnancy.
| S-EPMC4521125 | biostudies-literature