RESUMO
Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed 'DNAm GrimAge' has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (ß = -0.11), lower age 73 general cognitive ability (ß = -0.18), decreased brain volume (ß = -0.25) and increased brain white matter hyperintensities (ß = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.
Assuntos
Coorte de Nascimento , Epigênese Genética , Idoso , Envelhecimento/genética , Encéfalo/diagnóstico por imagem , Criança , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica , HumanosRESUMO
OBJECTIVES: Non-genetic risk factors for Sjögren's syndrome (SS) are poorly understood. Adherence to a Mediterranean diet has been associated with reduction in other autoimmune diseases. We examined the association of Mediterranean diet with SS. METHODS: New patients attending a single centre warranting investigation for primary SS (pSS) were recruited into the Optimising Assessment in Sjögren's Syndrome cohort established in Birmingham, UK (2014-2018). Participants were classified into pSS and non-SS sicca, considered as cases and non-cases, respectively, and asked to complete an optional food frequency questionnaire on their diet before onset of symptoms. A semi-quantitative Mediterranean diet score (MDS) was calculated (possible range=0 to 18). Using multivariate logistic regression, corrected for energy intake, body-mass index, sex, age, symptom duration, and smoking status, we examined the association of MDS with SS. RESULTS: Dietary data were available for 133/243 (55%) eligible patients (n=82 pSS and n=51 sicca). In the adjusted model, a higher total MDS (mean ± SD, 9.41±2.31 points) was associated with lower odds of pSS (OR 0.81, 95% CI 0.66-0.99; p=0.038) per one unit of MDS. Among MDS components, the strongest association was seen with fish with OR 0.44 (95% CI 0.24-0.83; p=0.01) in the comparison between <1 portion/week and 1 to 2.5 portions/week. Higher galactose, vitamin A-retinol-equivalents and vitamin C showed associations with lower odds of pSS in multivariate analysis, where the association of vitamin C was attenuated when adjusted for MDS. CONCLUSIONS: When adjusted for potential confounders, adherence to the Mediterranean diet was associated with lower likelihood of having pSS.
Assuntos
Dieta Mediterrânea , Síndrome de Sjogren , Índice de Massa Corporal , Estudos de Coortes , Humanos , Modelos Logísticos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/prevenção & controleRESUMO
OBJECTIVES: Given the similarity in symptoms between primary Sjogren's syndrome (SjS) and non-SjS sicca syndrome (sicca), we sought to characterise clinical and proteomic predictors of symptoms in both groups in order to better understand disease mechanisms and help guide development of immunomodulatory treatments. These have not, to date, unequivocally improved symptoms in SjS clinical trials. METHODS: Serum proteomics was performed using O-link inflammation and cardiovascular II panels. SjS (n=53) fulfilled 2016 ACR/European Alliance of Associations for Rheumatology (EULAR) criteria whereas sicca (n=60) were anti-Ro negative, displayed objective or subjective dryness, and either had a negative salivary gland biopsy or, in the absence of a biopsy, it was considered that a biopsy result would not change classification status. Linear regression analysis was performed to identify the key predictors of symptoms. Cluster analysis was completed using protein expression values. RESULTS: EULAR-Sjögren's-Syndrome-Patient-Reported-Index (ESSPRI), EuroQoL-5 Dimension utility values, and anxiety and depression did not differ between SjS and sicca. Correlations between body mass index (BMI) and ESSPRI were found in sicca and to a lesser extent in SjS. Twenty proteins positively associated with symptoms in sicca but none in SjS. We identified two proteomically defined subgroups in sicca and two in SjS that differed in symptom burden. Within hierarchical clustering of the SjS and sicca pool, the highest symptom burden groups were the least distinct. Levels of adrenomedullin (ADM), soluble CD40 (CD40) and spondin 2 (SPON2) together explained 51% of symptom variability in sicca. ADM was strongly correlated with ESSPRI (spearman's r=0.62; p<0.0001), even in a multivariate model corrected for BMI, age, objective dryness, depression and anxiety scores. CONCLUSIONS: Obesity-related metabolic factors may regulate symptoms in sicca. Further work should explore non-inflammatory drivers of high symptom burden in SjS to improve clinical trial outcomes.
Assuntos
Reumatologia , Síndrome de Sjogren , Ansiedade/etiologia , Proteínas da Matriz Extracelular/uso terapêutico , Humanos , Proteínas de Neoplasias/uso terapêutico , Proteômica , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológicoRESUMO
Periodontitis and gingivitis remain two of the most common diseases that affect the oral cavity. As they are caused by plaque, effective oral hygiene, elimination of plaque-retentive factors and successful periodontal treatment will result in resolution of gingival and periodontal inflammation. Certain systemic diseases can have a clinical appearance similar to periodontal diseases or exacerbate existing periodontitis/gingivitis and vice versa. This paper aims to provide the dental practitioner with an understanding of the manifestations of systemic diseases to the periodontium and highlights elements in the clinical assessment, which will aid in establishing a correct diagnosis. Additional anamnestic and clinical clues are important for distinguishing between plaque-induced and non-plaque-induced lesions. The first part of this compendium covers immune-mediated and hereditary conditions as causes of gingival lesions, which can resemble those caused by dental plaque. The different conditions are presented concisely and exemplified by clinical photographs. Dental practitioners should be aware of the various manifestations of systemic diseases to the periodontium in order to offer appropriate diagnosis and treatment, which can reduce both patient morbidity and mortality.
Assuntos
Placa Dentária , Gengivite , Doenças Periodontais , Periodontite , Humanos , InflamaçãoRESUMO
Periodontitis and gingivitis are highly prevalent inflammatory diseases of the oral cavity, and typically are characterised by the presence of dental plaque. However, other causes of oral inflammation exist, which can resemble plaque-induced gingivitis and periodontitis, and may thus first be seen by a dental practitioner. This paper aims to provide dentists with an understanding of the manifestations of systemic diseases to the periodontium and highlights anamnestic and clinical clues important for distinguishing between plaque-induced and non plaque-induced lesions. In the first part of this series immune-mediated and hereditary conditions as causes of gingival lesions were discussed; this second part highlights cancer-related gingival lesions as well as those caused by specific pathogens, medication or malnutrition. A clear clinical, epidemiological and visual overview of the different conditions is provided. Early diagnosis of non plaque-related causes of gingival lesions can be vital for affected patients. Therefore, dental practitioners should be aware of the various manifestations of systemic diseases to the periodontium.
Assuntos
Gengivite , Neoplasias , Doenças Periodontais , Odontólogos , Humanos , InflamaçãoRESUMO
BACKGROUND: DNA methylation levels change along with age, but few studies have examined the variation in the rate of such changes between individuals. METHODS: We performed a longitudinal analysis to quantify the variation in the rate of change of DNA methylation between individuals using whole blood DNA methylation array profiles collected at 2-4 time points (N = 2894) in 954 individuals (67-90 years). RESULTS: After stringent quality control, we identified 1507 DNA methylation CpG sites (rsCpGs) with statistically significant variation in the rate of change (random slope) of DNA methylation among individuals in a mixed linear model analysis. Genes in the vicinity of these rsCpGs were found to be enriched in Homeobox transcription factors and the Wnt signalling pathway, both of which are related to ageing processes. Furthermore, we investigated the SNP effect on the random slope. We found that 4 out of 1507 rsCpGs had one significant (P < 5 × 10-8/1507) SNP effect and 343 rsCpGs had at least one SNP effect (436 SNP-probe pairs) reaching genome-wide significance (P < 5 × 10-8). Ninety-five percent of the significant (P < 5 × 10-8) SNPs are on different chromosomes from their corresponding probes. CONCLUSIONS: We identified CpG sites that have variability in the rate of change of DNA methylation between individuals, and our results suggest a genetic basis of this variation. Genes around these CpG sites have been reported to be involved in the ageing process.
Assuntos
Metilação de DNA/genética , Idoso , Idoso de 80 Anos ou mais , Ilhas de CpG/genética , Feminino , Genoma Humano , Genótipo , Humanos , Padrões de Herança/genética , Masculino , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
We report a case of metastatic mesothelioma presenting as an oral metastasis in a 46-year-old patient. The patient presented with 2 polypoid lesions that appeared to be benign on the dorsum of the tongue. Excisional biopsy showed the presence of metastatic carcinoma that on further investigation proved to be mesothelioma. The initial presentation of mesothelioma as an oral metastasis is not previously reported. This article highlights the importance of biopsy and histopathological diagnosis in presumed benign lesions and the role of the general dental practitioner in screening for oral neoplasms.