Editors' ChoiceAging

Delaying methylation drift with diet

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Science Translational Medicine  04 Oct 2017:
Vol. 9, Issue 410, eaap8162
DOI: 10.1126/scitranslmed.aap8162


Aging related DNA methylation drift is delayed by a calorically restricted diet.

Regulation of gene expression occurs on many levels between the transcription and translation of mRNA. One such mechanism controlling transcription is through epigenetic chemical modifications to DNA and DNA associated binding proteins. Changes in methylation status at CpG islands in different cells and tissues are influenced by intrinsic and extrinsic factors. Aging is one such factor influencing hypo- and hypermethylation drift. Although methylation drift is associated with aging related changes in gene expression, it is not known if it directly correlates with expected life span or if antiaging interventions can delay or reverse its presence.

In the recent study by Maegawa et al., aging related methylation drift in blood cells was analyzed across mammalian species as a function of expected lifespan. Rates of change in the methylation status at specific loci during aging were found to be higher in the shorter-lived mice and lower in the longer-lived monkeys and humans. Thus, methylation drift is inversely proportional to expected life span. Applying caloric restriction without malnutrition, one of the most potent and well-studied interventions to delay the onset of aging, resulted in delays in DNA methylation drift in the blood cells of mice and monkeys. Expanding these findings, the authors were able to utilize DNA methylation as a predictor of biological age. They found that mice under caloric restriction with an average chronological age of 2.8 years had a methylation or biological age of only 0.8 years. Similarly, the average chronological age for the monkeys was 27 years, with those undergoing caloric restriction having a biological age of only 20 years.

Thus, detection of DNA methylation drift has the potential of being a powerful aging research tool. Further studies, particularly using humans on caloric restriction diets or other antiaging interventions, will be needed before these technologies and methodologies can be applied for clinical diagnostics.

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