Aging is a predominant risk factor for numerous chronic diseases that limit healthspan 1. Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues 2-10 , which supports a Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Aging is a multifactorial phenotype characterized by physiological changes with multifaceted effects or alterations causing gradual functional decline in a living organism (López-Otín et al., 2013). These age-associated alterations are also risk factors for various complex diseases such as cancer, diabetes, cardiovascular, and neurodegenerative diseases (López-Otín et al., 2013). Given its complex nature, the biology of aging has not been completely elucidated yet (Partridge, 2010). A number of genes and proteins in diverse biologic pathways have been implicated in influencing aging and longevity (Johnson et al., 1999). Some of the mechanisms that have

DNA methylation has been implicated in the etiopathology of various complex disorders. DNA methyltransferases are involved in maintaining and establishing new methylation patterns. The aim of the present study was to investigate the inherent genetic variations within DNA methyltransferase genes in predisposing to susceptibility to schizophrenia. We screened for polymorphisms in DNA methyltransferases, DNMT1, DNMT3A, DNMT3B and DNMT3L in 330 schizophrenia patients and 302 healthy controls for association with Schizophrenia in south Indian population. These polymorphisms were also tested for subgroup analysis with patient's gender, age of onset and family history. DNMT1 rs2114724 (genotype P = .004, allele P = 0.022) and rs2228611 (genotype P = 0.004, allele P = 0.022) were found to be significantly associated at genotypic and allelic level with Schizophrenia in South Indian population. DNMT3B rs2424932 genotype (P = 0.023) and allele (P = 0.0063) increased the risk of developing schizophrenia in males but not in females. DNMT3B rs1569686 (genotype P = 0.027, allele P = 0.033) was found to be associated with early onset of schizophrenia and also with family history and early onset (genotype P = 0.009). DNMT3L rs2070565 (genotype P = 0.007, allele P = 0.0026) confers an increased risk of developing schizophrenia at an early age in individuals with family history. In-silico prediction indicated functional relevance of these SNPs in regulating the gene. These observations might be crucial in addressing and understanding the genetic control of methylation level differences from ethnic viewpoint. Functional significance of genotype variations within the DNMTs indeed suggest that the genetic nature of methyltransferases should be considered while addressing epigenetic events mediated by methylation in Schizophrenia.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

ObjectiveTo examine polygenic inheritance of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of subjective cognitive complaints and slow gait.MethodsWe analyzed 4,915 individuals, age 65 years and above, with European ancestry (mean age 75.0 ± 6.8 years, 56.6% women) in the Health and Retirement Study. Polygenic scores (PGS) were calculated as weighted sums of the effect of single nucleotide polymorphisms, with effect sizes derived from genome-wide association studies. The association between PGSs of 9 phenotypes (general cognition, body mass index [BMI], mean arterial pressure, education, Alzheimer disease [AD], neuroticism, well-being, waist circumference, and depressive symptoms) and MCR as well as its key components (cognitive complaints and slow gait) were examined by logistic regression, adjusting for age, sex, education, and genetic ancestry, and reported as odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThere were 260 prevalent MCR cases, 529 with slow gait, and 1,928 with subjective cognitive complaints. Higher PGSs for BMI (OR 1.22, 95% CI 1.07–1.39) and waist circumference (OR 1.23, 95% CI 1.07–1.40) were associated with MCR, and PGS of AD showed a suggestive association (OR 1.16, 95% CI 1.02–1.32). Higher PGS for neuroticism (OR 1.10, 95% CI 1.03–1.18) was associated with cognitive complaints, whereas higher well-being PGS (OR 0.92, 95% CI 0.87–0.98) was protective. PGS for BMI (OR 1.16, 95% CI 1.06–1.28), waist circumference (OR 1.19, 95% CI 1.08–1.31), and AD (OR 1.13, 95% CI 1.03–1.24) was associated with slow gait.ConclusionObesity-related genetic traits increase risk of MCR syndrome; further investigation is required to identify potential therapeutic targets.