Epigenetic variation during the adult lifespan: cross‐sectional and longitudinal data on monozygotic twin pairs
Open Access
- 23 May 2012
- journal article
- research article
- Published by Wiley in Aging Cell
- Vol. 11 (4), 694-703
- https://doi.org/10.1111/j.1474-9726.2012.00835.x
Abstract
The accumulation of epigenetic changes was proposed to contribute to the age‐related increase in the risk of most common diseases. In this study on 230 monozygotic twin pairs (MZ pairs), aged 18–89 years, we investigated the occurrence of epigenetic changes over the adult lifespan. Using mass spectrometry, we investigated variation in global (LINE1) DNA methylation and in DNA methylation at INS, KCNQ1OT1, IGF2, GNASAS, ABCA1, LEP, and CRH, candidate loci for common diseases. Except for KCNQ1OT1, interindividual variation in locus‐specific DNA methylation was larger in old individuals than in young individuals, ranging from 1.2‐fold larger at ABCA1 (P = 0.010) to 1.6‐fold larger at INS (P = 3.7 × 10−07). Similarly, there was more within‐MZ‐pair discordance in old as compared with young MZ pairs, except for GNASAS, ranging from an 8% increase in discordance each decade at CRH (P = 8.9 × 10−06) to a 16% increase each decade at LEP (P = 2.0 × 10−08). Still, old MZ pairs with strikingly similar DNA methylation were also observed at these loci. After 10‐year follow‐up in elderly twins, the variation in DNA methylation showed a similar pattern of change as observed cross‐sectionally. The age‐related increase in methylation variation was generally attributable to unique environmental factors, except for CRH, for which familial factors may play a more important role. In conclusion, sustained epigenetic differences arise from early adulthood to old age and contribute to an increasing discordance of MZ twins during aging.Keywords
This publication has 48 references indexed in Scilit:
- Tobacco-Smoking-Related Differential DNA Methylation: 27K Discovery and ReplicationAmerican Journal of Human Genetics, 2011
- A twin approach to unraveling epigeneticsTrends in Genetics, 2011
- Decline in genomic DNA methylation through aging in a cohort of elderly subjectsMechanisms of Ageing and Development, 2009
- Prospects for Epigenetic EpidemiologyAmerican Journal of Epidemiology, 2008
- Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPARα promoter of the offspringBritish Journal of Nutrition, 2008
- Intra-individual Change Over Time in DNA Methylation With Familial ClusteringJAMA, 2008
- Cytosine methylation profiling of cancer cell linesProceedings of the National Academy of Sciences of the United States of America, 2008
- Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndromeProceedings of the National Academy of Sciences of the United States of America, 2006
- DNA methylation profiling of human chromosomes 6, 20 and 22Nature Genetics, 2006
- A twin-pronged attack on complex traitsNature Genetics, 1997