Abstract
Alu hypomethylation promotes genomic instability and is associated with aging and age-related diseases. Dietary factors affect global DNA methylation, leading to changes in genomic stability and gene expression with an impact on longevity and the risk of disease. This preliminary study aims to investigate the relationship between nutritional factors, such as circulating trace elements, lipids and antioxidants, and Alu methylation in elderly subjects and offspring of healthy nonagenarians. Alu DNA methylation was analyzed in sixty RASIG (randomly recruited age-stratified individuals from the general population) and thirty-two GO (GeHA offspring) enrolled in Italy in the framework of the MARK-AGE project. Factor analysis revealed a different clustering between Alu CpG1 and the other CpG sites. RASIG over 65 years showed lower Alu CpG1 methylation than those of GO subjects in the same age class. Moreover, Alu CpG1 methylation was associated with fruit and whole-grain bread consumption, LDL2-Cholesterol and plasma copper. The preserved Alu methylation status in GO, suggests Alu epigenetic changes as a potential marker of aging. Our preliminary investigation shows that Alu methylation may be affected by food rich in fibers and antioxidants, or circulating LDL subfractions and plasma copper.
Highlights
DNA methylation represents an epigenetic mechanism involved in the regulation of several biological processes, including gene expression, genomic stability and parental imprinting [1]
Previous studies reported an age-dependent decline in genomic DNA methylation, both in global DNA and in Alu elements [13,14,17]
We observed that Alu methylation at the CpG1 site do not display marked age-related changes, but lower levels of methylation at this site were found in elderly subjects over 65 years compared to the age class 55–64 years
Summary
DNA methylation represents an epigenetic mechanism involved in the regulation of several biological processes, including gene expression, genomic stability and parental imprinting [1]. Most of DNA methylation in human genomic DNA occurs in the repetitive sequences, among which the Alu elements (short-interspersed nuclear elements with a length of about 300 bp) represent approximately. 11% of the genome and contains 23% of its methylation sites [2,3,4] Based on their evolutionary history, Alu elements are divided in subfamilies of different evolutionary age, classified in the major groups. In normal tissues most Alu elements are methylated and transcriptionally inactive [9,10]. This condition has been proven to stabilize the genome by preventing accumulation of DNA damage [11], whereas hypomethylation of Alu elements is associated with genomic instability [12]
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