Famine, Epigenetics, and Long-Term Health: Implications for Gaza

Prolonged periods of famine have been linked to a number of long-term physical health issues beyond those related to immediate malnutrition. The evidence of this has accumulated over several decades of study, showing that nutritional deficiencies during the critical periods of development can cause alterations in gene expression through changes in mechanisms of epigenetics (DNA methylation, histone modification, and non-coding RNA), which could be maintained across an individual's life span and may contribute to health problems in future generations. This literature review will examine the available evidence from major historical famine cohorts, including the Dutch Hunger Winter, the Chinese Great Famine, and the Leningrad Siege, as well as experimental studies utilizing animal models. Together, the results of all of these studies suggest that there is an association between early-life nutritional deprivations and altered regulation of genes responsible for growth, metabolism, and stress response, especially IGF2 and NR3C1. This review will also explore whether these results are relevant to current-day food shortages and maternal-child malnutrition occurring in Gaza. Gaza-related discussions within this manuscript are presented as a risk-based extrapolation of historical cohorts rather than a predictive model for expected outcomes due to the lack of Gaza population-specific epigenetic studies and the many confounders present, including but not limited to trauma exposure, infectious disease, displacement, and disrupted access to healthcare. While there is substantial evidence supporting the biological plausibility of maintaining epigenetic changes resulting from famine exposures, there are still a number of important limitations regarding making causative inferences about the exposure, measuring exposure, and how much of the epigenetic changes are transmitted between generations in humans. As such, this review will conclude that providing early nutritional and psychosocial interventions may offer some protection against long-term health risks and emphasize the necessity of continued research into the effects of famine and other forms of extreme hardship and trauma in conflict-affected areas.