Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder

Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out.From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure.The association of trauma with telomere length was in the expected direction but not significant (. B=. -10.2, p=. 0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (. B=. 1.91, p=. 0.018). In concordance, trauma significantly accelerated epigenetic ageing (. B=. 1.97, p=. 0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (. B=. -0.10, p=. 0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results.Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic ageing. These findings warrant further study of a perhaps dysfunctional compensatory cellular ageing reversal in PTSD

Quantification of Double Stranded DNA Breaks and Telomere Length as Proxies for Corneal Damage and Replicative Stress in Human Keratoconus Corneas

Purpose: The pathogenesis of keratoconus (KC) is multifactorial, and associated with oxidative stress and subsequent DNA damage. We investigate differences in DNA damage and replicative stress in patients with KC, and in healthy and diseased controls. Methods: We obtained 64 corneal buttons from 27 patients with KC after corneal transplant surgery, 21 with a decompensated graft (DG), and 16 healthy controls (HC). The amount of intact Alu elements per genome copy as measured by quantitative polymerase chain reaction (qPCR) was used to quantify intact DNA. Telomere length was measured as a proxy for replicative stress. In addition, telomerase reverse transcriptase (hTERT) gene expression level was assessed. Results: Mean (6 standard deviation [SD]) DNA damage was similar between the KC (5.56 6 14.08), DG (3.16 6 8.22), and HC (3.51 6 6.66) groups (P = 0.807). No associations were found between DNA damage and patient age (P = 0.523), atopic constitution (P = 0.240), or contact lens wear (P = 0.393). Telomere length differed (P = 0.034), most notably in the KC group, and hTERT was not detected in any corneal sample. Three cross-linked (CXL) KC corneas did not contain significantly more DNA damage (☓2.6, P = 0.750). Conclusions: Based on these findings, differences in actual corneal DNA damage in KC could not be identified, and the longer telomere length in KC did not support replicative stress as a major etiologic factor in the pathogenesis of KC. Future longitudinal investigations on KC etiology should assess progressively early cases to better comprehend the cellular and molecular processes preceding the archetypical morphologic changes. Translational Relevance: The standard treatment for progressive keratoconus promotes the crosslinking of collagen fibers through ultraviolet radiation and the subsequent formation of reactive oxygen species. Our study helps to underline the safety of this treatment approach

Genome-wide association scan in systemic sclerosis identifies MHC region and two additional susceptibility loci On 2q32 and 7q32

Purpose: Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs that leads to profound disability and premature death. Accumulating evidence point to a strong genetic component that is underlying the susceptibility of SSc. Here we aimed to identify the genetic factors that underly SSc. Method & Results: To identify the genetic traits for SSc, we performed a genome-wide association study comparing 842 European Caucasian SSc cases with 1711 European Caucasian controls exploiting the Illumina human BeadChip. Using a replication cohort comprising 1640 European Caucasian SSc cases and 1700 controls matched for country of origin we aimed to replicate the 11 most strongly non-MHC associated SNPs in the GWAS and replicated the association of STAT4 (P = 4.03E-10). After stratification for SSc phenotype, significant association (

Telomere quantification in frontal and temporal brain tissue of patients with schizophrenia

Recent imaging studies have suggested that accelerated aging occurs in schizophrenia. However, the exact cause of these findings is still unclear. In this study we measured telomere length, a marker for cell senescence, in gray and white matter brain tissue from the medial frontal gyrus (MFG) and superior temporal gyrus (STG) of 9 patients with schizophrenia and 11 controls. No alterations in telomere length were found in MFG gray and white matter and in STG gray matter. A significant reduction in telomere length was observed in STG white matter of patients with schizophrenia as compared to controls (fold change of −0.42, U = 5, P = 0.008). Our results support previous findings that telomere length in gray matter is not affected, whereas they suggest that increased cell senescence may affect white matter temporal brain tissue

Beneficis de l’activitat física moderada aquàtica i terrestre, tant per a la dona gestant com per al fetus, durant l’embaràs

[cat] L’activitat física durant l’embaràs té molts beneficis, tant per a la dona gestant com per al fetus. En el procés de gestació el cos de la dona experimenta una sèrie de canvis anatòmics, fisiològics i emocionals. Davant aquestes modificacions es planteja el dubte de quin tipus d’activitat física és més adequada per a les embarassades i per als fetus. S’ha realitzat una revisió sistemàtica dels darrers 10 anys, identificant els millors articles de la literatura que aporten evidència científica respecte a aquest tema. L’objectiu d’aquest treball de fi de grau és identificar quins beneficis aporta la realització d’activitat física moderada durant l’embaràs, tant per a la dona gestant com per al fetus, i analitzar quin tipus d’exercici físic és més adequat durant la gestació, el que es desenvolupa en medi aquàtic o en medi terrestre. Es pot afirmar que l’activitat física moderada en medi aquàtic és més beneficiosa per a la dona embarassada i per al fetus. Entre els principals beneficis que aporta la realització d’activitat física durant l’embaràs trobem la prevenció d’augment de pes de l’embarassada, la prevenció de la diabetis mellitus gestacional, disminució de la lumbàlgia, prevenció de la depressió postpart, prevenció dels trastorns del son, ajuda a combatre la fatiga causada per l’embaràs, disminució de l’edema, prevenció de la preclàmpsia, augmenta la força dels músculs del sòl pelvià evitant així els trastorns que hi ha associats com la incontinència urinària, disminució del nombre d’episiotomies i de cesàries, entre d’altres