Aging, Environment, & DiseaseDNA Methylation and Hydroxymethylation

Does Epigenetics Control Aging? New study finds DNA methylation patterns change with age

Aging is a natural part of life, but many of the molecular details that contribute to the aging process remain unclear and cannot be explained by classical genetics.  There are several age-related DNA methylation biomarkers, suggesting that epigenetics is involved in aging, but until recently there has not been a systematic genome-wide approach to investigate the link between DNA methylation and aging.

In a recent report in PNAS, Heyn et al. performed whole-genome bisulfite sequencing (WGBS) on genomes from CD4+ T cells from both a newborn baby and a 103-year-old man (centenarian).  The authors found that there were significantly lower levels of DNA methylation in the 103-year-old man relative to the newborn across the entire genome (73% of all CpG sites were methylated in the centenarian compared to 80.5% in the newborn).  The greatest differences in DNA methylation levels in genetic regulatory regions were at the promoters for genes that contain few CpG sites and at tissue-specific genes, which were both significantly hypomethylated in the centenarian.  These results suggest that genes typically silenced or expressed at low levels in newborns are expressed to higher levels in older people, providing a possible molecular mechanism for some age-related diseases.  Many of the differentially methylated regions (DMRs) between the newborn and the centenarian were at repeated DNA elements such as LINE repeats, Alu repeats, mammalian interspersed repeats (MIRs), and retrotransposons, with the centenarian genome showing decreased DNA methylation and correspondingly increased transcription from these regions.  These results suggest that the regulation of transcription from repetitive DNA elements, once thought to be “junk DNA”, might be important to human health.  Similar findings were observed when the authors extended their study to include more newborn and old individuals.  The researchers also observed an intermediate level of DNA methylation relative to the newborn and the centenarian (77.8% methylated) in a man that was intermediate in age (26 years old), further enforcing the notion that the global DNA methylation pattern changes with age.

The findings in this article strongly suggest that there is an epigenetic component to aging and opens the door to the possibility of treating age-related diseases by targeting epigenetic mechanisms.  While more work needs to be done to further elucidate the role of DNA methylation in aging, this study strengthens the connection between epigenetics and its affect on aging.  What role do you think DNA methylation is playing in the aging process?

Heyn HLi NFerreira HJMoran SPisano DGGomez ADiez JSanchez-Mut JVSetien FCarmona FJPuca AASayols SPujana MASerra-Musach J, Iglesias-Platas IFormiga FFernandez AFFraga MFHeath SCValencia AGut IGWang JEsteller M.  (2012)  Distinct DNA methylomes of newborns and centenarians.  Proc Natl Acad Sci U S A.  Jun 11. [Epub ahead of print]

Article is freely available online through the PNAS open access option:  http://www.pnas.org/content/early/2012/06/05/1120658109.full.pdf

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Kevin B.

Kevin B.

Kevin grew up in Northern California and has also spent several years living on the East Coast. When he is not in the lab, Kevin enjoys snowboarding, watching NFL games (and playing fantasy football!), spending time outdoors, and exploring Southern California.