Early Life Nutrition, Epigenetics and Programming of Later Life Disease

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by Shea Robison (@EpigeneticsGuy)

Early Life Nutrition, Epigenetics and Programming of Later Life Disease

Author: Mark H. Vickers

Journal: Nutrient

Publication Date: June 2, 2014

Affiliation: Liggins Institute and Gravida, National Centre for Growth and Development, University of Auckland, 85 Park Road, Grafton, Auckland 1142, New Zealand

Policy Implications: This paper is a review of the human and animal studies of epigenetic changes in early development – many of which can be passed on to multiple generations – which manifest as metabolic conditions later in life. Some of the conditions in the studies which are cited which contribute to increased incidence of metabolic disorders in later life are maternal nutrition and paternal obesity at the time of conception. Therefore, the most obvious policy implications from the research cited in this review are for obesity policy: That circumstances such as maternal nutrition and paternal weight – which are ostensibly under the control of the parents – are found to be such significant factors in the subsequent metabolic diseases of their offspring provides support for obesity prevention policies which focus on the behavior and choices of the parents. However, this focus on the choices and behaviors of parents as a matter of policy raises all sorts of personal liberty and individual freedom issues which would also need to be addressed, especially in  political cultures like that of the United States which emphasize individualism and personal responsibility.

Summary: This paper is a review of the contemporary work being done on epigenetic changes in early development which manifest as metabolic conditions later in life. As such, it is a good source for recent research on this topic.

As the author writes, there is a substantial body of work in epigenetics on the effects on fetal and post-natal development of methylation or demethylation resulting from maternal nutrition, levels of maternal care, and other environmental conditions. This paper focuses on the phenotypic effects of epigenetic modifications during these developmental stages which manifest as metabolic conditions such as obesity and metabolic diseases such as Type 2 diabetes much later in the life cycle. The author presents evidence from human epidemiology and animal models, and discusses transgenerational epigenetic programming in particular as an example of the long-term effects of epigenetic modifications in early development.

In regards to human epidemiology, the author acknowledges that the evidence linking these epigenetic changes to metabolic diseases later in life is limited for humans, but cites evidence for the inheritance of tissue-specific DNA methylation patterns. The author also refers to studies which have found epigenetic differences between twins related to life history, and to studies on the Dutch Hunger Winter (1944-1945) cohort in which significant epigenetic changes in later life have been correlated with different early developmental stages during the famine. The author also mentions that while macronutrients have been implicated in such changes, maternal micronutrient levels (such as vitamin B12) are of particular interest, as is parental obesity at the time of conception.

In reference to the animal studies, the author cites the substantial evidence that has been gathered for the manifestation of these early epigenetic changes in later life. As cited by the author, researchers have extensively studied the effects of maternal undernutrition, restricted intrauterine growth, and paternal obesity in animals. The author also summarizes different intervention strategies studied by epigeneticists “to ameliorate or reverse the effects” of this early developmental programming. These include neonatal leptin treatments, remethylation via dietary intake, and exercise, which have all been shown to change DNA methylation in ways which reduce or prevent subsequent manifestation of these metabolism-related disorders.

Evidence of the transgenerational inheritance of acquired characteristics is perhaps the most interesting and the most controversial results of research in epigenetics. As the author notes, there is substantial evidence for both the germline and somatic inheritance of non-genetic traits, and that the transgenerational inheritance of these non-genetic traits has the potential to “result in a population-wide manifestation of a phenotype over several generations,” and that “such transmission can exacerbate the rapid onset of phenotypes such as obesity and diabetes currently observed in human populations.”  The author reviews a number of studies which show the non-genetic transmission of traits to the F1 generation, and some which show such inheritance to the F2 generation and even the F3 generation. However, the author also cites a meta-analysis of nine transgenerational studies which were carried through to F3, and that five of these studies failed to show any effect. Again, though, paternal nutrition and paternal obesity are both shown to initiate transgenerationally-inherited epigenetic changes.

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