Abstract
Epidemiologic studies on A-bomb survivors indicate a significant increase of non-cancer risks (mainly life-style diseases). However, since no animal models are known, understanding of the biological mechanisms is slow. Here, I propose possible mechanisms that are biologically testable.
Low birth weight has been indicated as one of the risk factors for coronary heart disease, hypertension, and type II diabetes later in life, which raises a possibility that a part of life-style disease risk starts from fetal life. This observation is interpreted as that when nutrition level to fetuses was insufficient, babies are born small and acquire thrifty phenotype after birth as a result of adaptation. This phenotype is considered to be beneficial if the postnatal food conditions are suboptimal whereas if not it can lead to elevated risk of life-style diseases.
Two explanations are proposed; 1) Insufficient tissue recovery: it is possible that tissue recovery is not perfect. For example, insufficient cell number in pancreas can lead to suboptimal production of insulin years later. 2) Hypomethylation of DNA: Avy(viable yellow) allele in the mouse is due to insertion of a retrotransposon (RT), which gives rise to a wide interindividual variation in methylation at RT sequences (dark brown = methylation, yellow = hypomethylation). When methyl-rich diet is given to pregnant mothers, the offspring becomes darker color and healthier. By contrast, radiation exposure and malnutrition may cause the opposite effect.
