First brought to scientific attention several decades ago by the report of a dose-response, inverse relation between birth weight and adult risk of cardiometabolic diseases (1), evidence that early nutrition, stress, and other similar environmental exposures can have lingering impacts on later health outcomes has now been widely documented in human populations and in experimental animal model work (2). A central problem in this field is identifying the mechanisms that underlie the biological "memory" of early nutrition and other exposures. Early proposals focused on growth alterations or changes in the function of organs such as the kidneys or liver, which it was speculated would be short-changed under conditions of fetal nutritional stress. Although this likely helps to explain some of the human findings (3), more recent work has consolidated around identifying epigenetic changes induced by prenatal or maternal experiences, which provide particularly attractive candidates (4, 5). Epigenetic modifications typically involve chemical changes to the chromatin that influence which genes can be expressed, silencing or amplifying gene production in a targeted fashion. DNA methylation refers to the addition of a methyl group to cytosine nucleotides in the vicinity of a gene promoter, which impedes gene transcription. It is among the best studied of epigenetic processes and one that is chemically stable enough to potentially account for late-life effects of early nutrition.
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