Chromatin Structure from Development to Ageing.

Nuclear structure influences genome architecture, which contributes to determine patterns of gene expression. Global changes in chromatin dynamics are essential during development and differentiation, and are one of the hallmarks of ageing. This chapter describes the molecular dynamics of chromatin structure that occur during development and ageing. In the first part, we introduce general information about the nuclear lamina, the chromatin structure, and the 3D organization of the genome. Next, we detail the molecular hallmarks found during development and ageing, including the role of DNA and histone modifications, 3D genome dynamics, and changes in the nuclear lamina. Within the chapter we discuss the implications that genome structure has on the mechanisms that drive development and ageing, and the physiological consequences when these mechanisms fail.

Serum Levels of Glial Fibrillary Acidic Protein Association with Cognitive Impairment and Type 2 Diabetes.

BACKGROUND: Peripheral biomarkers associated with neurocognitive disorders (NCD) have been evaluated in an attempt to improve diagnosis and early detection and potentially even prevent them. Along with increasing age, type 2 diabetes (T2D) increases the risk of central nervous system disorders and cognitive impairment due to the loss of synaptic function. Central damage triggers an astroglial response, increasing the expression of glial fibrillary acidic protein (GFAP), which can be found peripherally when the blood-brain barrier is compromised. AIM OF THE STUDY: To evaluate the value of GFAP as a peripheral biomarker of central dysfunction. METHODS: Serum levels of GFAP were compared between cases of NCD (n = 69) and age-matched controls (n = 69), analyzing the influence of diabetes as contributing factor. RESULTS: We found higher levels of serum GFAP in subjects with NCD compared with the control group (p <0.0001). The receiver operating characteristic (ROC) curve using the GFAP levels showed 65.22% sensitivity and 71.01% specificity (AUC = 0.7608), indicating good performance in the classification of controls and NCD patients. Logistic regression indicated a positive predictive power of 67.50% considering T2D status; adding GFAP levels, the predictive power rises to 71.93%. GFAP levels and T2D could be considered good predictors of NCD risk. CONCLUSIONS: Our findings open the possibility that peripheral GFAP could be used as an objective measurement related, under certain conditions, to central damage; thereby serving as a follow-up marker to refer diabetic patients for appropriate neurological evaluation, which could offer a low cost, minimally invasive strategy to improve the assessment of cognitive affectation and subsequent treatment.