An epigenome-wide association study of waist circumference in Chinese monozygotic twins.

OBJECTIVES: Central obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships. METHODS: A total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage. RESULTS: We identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites. CONCLUSIONS: Our research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

Effect of (m)VD-hemopressin against Aß1-42-induced oxidative stress and apoptosis in mouse hippocampal neurons.

Alzheimer's disease (AD) is a serious neurodegenerative disease. Senile plaques (SPs) composed of amyloid-ß (Aß) are typical features of AD. Aß plays a key role in the disease and has the ability to induce other pathological characteristics of AD, including oxidative stress injury. (m)VD-hemopressin (VD), a peptide derived from mouse brain extracts, can bind cannabinoid 1 receptor (CB1R) as an agonist. Our previous report indicated that VD reverses memory impairment induced by Aß1-42 in mice. This study aimed to clarify the mechanism by which VD protects hippocampal neurons against Aß1-42-induced impairment. Our results showed that VD inhibited oxidative stress injury induced by Aß1-42, as demonstrated by the VD-induced reversal of the upregulation of reactive oxygen species (ROS) and the intracellular lipid peroxidation product malondialdehyde (MDA) and the downregulation of the activities of the antioxidative enzymes catalase (CAT) and glutathione peroxidase (GSH-PX) in mouse hippocampal neurons. We also found that VD restored the decrease in cell growth and viability induced by Aß1-42 and reversed Aß1-42-induced apoptosis mediated by the apoptosis-associated proteins Bcl-2 and Bax. However, cotreatment with AM251 (an antagonist of CB1R) blocked the effects of VD. In brief, this study suggested that through CB1R, VD reversed the impairment of cell growth and viability, oxidative stress injury and apoptosis induced by Aß1-42. Therefore, VD may be a promising agent for the treatment of diseases that involve oxidative stress injury and apoptosis induced by Aß1-42, such as AD.

Aerobic exercise-stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney.

Aerobic exercise induces many adaptive changes in the whole body and improves metabolic characteristics. Klotho, an anti-aging gene, is mainly expressed in the brain and kidney. The roles of Klotho in the brain and kidney during aerobic exercise remain largely unknown. The present study aimed to determine whether aerobic exercise could influence the expression of Klotho, decrease reactive oxygen species (ROS) and prolong life span. Sprague Dawley rats were exercised on a motor treadmill. Klotho mRNA and protein expression levels in rat brain and kidney tissues were examined using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. ROS production was detected following intermittent aerobic exercise (IAE) or continuous aerobic exercise (CAE). Kaplan-Meier curve analysis demonstrated that aerobic exercise significantly improved rat survival (P<0.001). The ROS levels in rat brain and kidney tissues were decreased in the aerobic exercise groups compared with the control group (P<0.05). In addition, Klotho mRNA and protein expression levels were increased significantly following aerobic exercise compared with controls (P<0.05). There was no significant difference between the IAE and CAE groups in any experiments (P>0.05). These results suggest that aerobic exercise-stimulated Klotho upregulation extends the life span by attenuating the excess production of ROS in the brain and kidney. As Klotho exhibits a potential anti-aging effect, promoting Klotho expression through aerobic exercise may be a novel approach for the prevention and treatment of aging and aging-related diseases.