Lejarraga Horacio
Universidad de Buenos Aires.
Arch Argent Pediatr. 2019 Jun 1;117(3):e232-e242. doi: 10.5546/aap.2019.eng.e232.
Three relevant, interrelated scientific advances are described: the concept of critical periods (CPs), the Barker Hypothesis (BH), and the underlying epigentic mechanisms involved. Critical periods are genetically programmed, highly sensitive time intervals during which the interaction between environment and individuals generates the development of physiological processes related to physical growth and development, survival (breastfeeding), social behavior, and learning. Barker hypothesis is based on the finding that prenatal malnutrition (for example, lowbirthweight) is closely related to mortality due to cardiovascular disease CVD) in the adult, and to the risk conditions leading to it: insuline resistence, metabolic syndrome, obesity, and high blood pressure. This association is no due to genetical causes, but secondary to nutritional deficits which in turn generate epigenetic mechanisms of methylation of DNA basis and cromatine proteines (histones), which do not modify the genetic code but modulate its expresion, reinforcing some genes, inhibiting others, regulating when and where they are expressed. These genes participate in the process called programming, consisting of permanent changes in the response to stimulation of metabolic and hormone regulators, such as, for example, increasing insuline resistence. Epigenetic changes persist even when original conditions (fetal or perinatal malnutrition) are no longer present. This, in turn, affects health of the offspring later in adult life, creating thus the same environmental prenatal conditions to the next generation. This transgenerational effects of early nutritional experiences are more frequent in population groups of por socioeconomic level, and consequently have serious implications in the future health of Latin American populations.
关键期(CPs)的概念、巴克假说(BH)以及相关的表观遗传机制。关键期是由基因编程的、高度敏感的时间间隔,在此期间,环境与个体之间的相互作用会引发与身体生长发育、生存(母乳喂养)、社会行为和学习相关的生理过程的发展。巴克假说基于这样的发现:产前营养不良(例如低出生体重)与成年人因心血管疾病(CVD)导致的死亡率密切相关,也与导致心血管疾病的风险因素有关,如胰岛素抵抗、代谢综合征、肥胖和高血压。这种关联并非由遗传原因引起,而是继发于营养缺乏,营养缺乏进而引发DNA碱基和染色质蛋白(组蛋白)甲基化的表观遗传机制,这些机制不会改变遗传密码,但会调节其表达,增强一些基因,抑制另一些基因,并调节它们何时何地表达。这些基因参与了所谓的编程过程,即代谢和激素调节因子对刺激的反应发生永久性变化,例如增加胰岛素抵抗。即使原始条件(胎儿期或围产期营养不良)不再存在,表观遗传变化仍然持续存在。这反过来又会影响后代成年后的健康,从而为下一代创造相同的产前环境条件。早期营养经历的这种跨代效应在社会经济水平较低的人群中更为常见,因此对拉丁美洲人群未来的健康具有严重影响。