title: Short-term calorie restriction ameliorates genomewide, age-related alterations in DNA methylation.
abstract: DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next-generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short-term calorie restriction (CR) on the methylome of aged rat kidney. Whole-genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4-week, short-term CR) rats was analyzed by methylated DNA immunoprecipitation and next-generation sequencing (MeDIP-Seq). CpG islands and repetitive regions were hypomethylated, but 5'-UTR, exon, and 3'-UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short-term CR could partially ameliorate age-related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease-related genes during aging may indicate increases in susceptibility to age-related diseases. Therefore, the CR-induced epigenetic changes that ameliorate age-dependent aberrant methylation may be important to CR's health- and life-prolonging effects.
authors: Genomictree Inc., Daejeon, Korea.
authors: Chul Hong
authors: CH
authors: Kim
authors: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors: Eun Kyeong
authors: EK
authors: Lee
authors: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors: Yeon Ja
authors: YJ
authors: Choi
authors: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors: Hye Jin
authors: HJ
authors: An
authors: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors: Hyeong Oh
authors: HO
authors: Jeong
authors: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea.
authors: Daeui
authors: D
authors: Park
authors: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea.
authors: Byoung Chul
authors: BC
authors: Kim
authors: Department of Physiology, University of Texas Health Science Center, San Antonio, TX, USA.
authors: Byung Pal
authors: BP
authors: Yu
authors: Biomedical Engineering, Ulsan National Institute of Sciences and Technology, Ulsan, Korea.
authors: Jong
authors: J
authors: Bhak
authors: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors: Hae Yung
authors: HY
authors: Chung
keywords: Bioinformatics; DNA methylation; MeDIP-Seq; aging; calorie restriction