Paternal and Chronological Age Effects on BEGAIN Methylation and Role in Autism | Aging-US



December 7, 2023

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  • Aging-US published this trending research paper on November 28, 2023, in Volume 15, Issue 22, entitled, “Effects of paternal and chronological age on BEGAIN methylation and its possible role in autism" by researchers from the Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany; Department of Bioinformatics, Julius Maximilians University, Würzburg, Germany; U.F. de Neurogénétique Moléculaire et Cellulaire, Dpt. de Génétique et Cytogénétique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Institute of Human Genetics, University Hospital Essen, Essen, Germany; College of Health and Life Sciences and College of Science and Engineering, Hamad Bin Khalifa University, Doha, Qatar; Fertility Center, Wiesbaden, Germany. DOI - Corresponding authors - Thomas Haaf - Abstract Children from old fathers carry an increased risk for autism spectrum (ASD) and other neurodevelopmental disorders, which may at least partially be mediated by paternal age effects on the sperm epigenome. The brain enriched guanylate kinase associated (BEGAIN) protein is involved in protein-protein interactions at and transmission across synapses. Since several epigenome-wide methylation screens reported a paternal age effect on sperm BEGAIN methylation, here we confirmed a significant negative correlation between BEGAIN promoter methylation and paternal age, using more sensitive bisulfite pyrosequencing and a larger number of sperm samples. Paternal age-associated BEGAIN hypomethylation was also observed in fetal cord blood (FCB) of male but not of female offspring. There was no comparable maternal age effect on FCB methylation. In addition, we found a significant negative correlation between BEGAIN methylation and chronological age (ranging from 1 to 70 years) in peripheral blood samples of male but not of female donors. BEGAIN hypomethylation was more pronounced in male children, adolescents and adults suffering from ASD compared to controls. Both genetic variation (CC genotype of SNP rs7141087) and epigenetic factors may contribute to BEGAIN promoter hypomethylation. The age- and sex-specific BEGAIN methylation trajectories in the male germ line and somatic tissues, in particular the brain, support a role of this gene in ASD development. Sign up for free Altmetric alerts about this article - Subscribe for free publication alerts from Aging - Keywords - aging, age and sex effect, autism spectrum disorder, BEGAIN, chronological aging, paternal age effect, sperm methylation About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ and connect with us: SoundCloud - Facebook - X - Instagram - YouTube - LinkedIn - Pinterest - Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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