UNC Nutrition Research Institute, Department of Nutrition, University of North Carolina at Chapel Hill, Kannapolis, NC, U.S.A.
Aging Dis. 2012 Dec;3(6):444-53. Epub 2012 Sep 27.
Multiple cues from the environment of our indirect and immediate ancestors, which often persist throughout the prenatal period and adulthood, are shaping our phenotypes through either direct, parent-to-child influences, or transgenerational inheritance. These effects are due to gene-environment interactions, which are intended to be a predictive tool and a mechanism of quick adaptation to the environment, as compared with genetic variations that are inherited over many generations. In certain circumstances the influences induced by the gene-environment interactions can have deleterious effects upon the health status, in the context of a radical change in the environment that does not fit with the predicted conditions, via epigenetic alterations. Conversely the best fit to the expected environment might have a delayed aging process and a longer life span. This review will touch upon the Developmental Origins of Health and Disease (DoHAD) concept, while discussing recent advances in the understanding of metabolic and cognitive disruptions, with a focus on epigenetic factors, their transgenerational effects, and the consequences they might have upon the onset of chronic disease and premature exitus.
多种来自间接和直接祖先环境的线索,这些线索常常在胎儿期和成年期持续存在,通过直接的、父母对子女的影响或跨代遗传来塑造我们的表型。这些影响是由于基因-环境相互作用所致,与遗传变异相比,基因-环境相互作用旨在成为一种预测工具和快速适应环境的机制,遗传变异是经过许多代遗传下来的。在某些情况下,基因-环境相互作用引起的影响可能会对健康状况产生有害影响,尤其是在环境发生剧烈变化而与预期条件不匹配的情况下,会通过表观遗传改变产生影响。相反,最适合预期环境的情况可能会导致衰老过程延迟和寿命延长。本文将讨论健康与疾病的发育起源(DoHAD)概念,同时讨论对代谢和认知障碍的最新理解,重点关注表观遗传因素、它们的跨代效应以及它们对慢性疾病和过早死亡的发生可能产生的后果。