Dirección de Investigación, Instituto Nacional de Geriatría, Mexico City 10200, Mexico.
Unidad de Investigación en Epidemiología, Instituto Nacional de Pediatría, Mexico City 04530, Mexico.
Exp Gerontol. 2022 Oct 1;167:111899. doi: 10.1016/j.exger.2022.111899. Epub 2022 Jul 28.
Barker's hypothesis affirms that undernourishment in early-life induces metabolic reprogramming that compromises organism functions later in life, leading to age-related diseases. We are exposed to environmental and social conditions that impact our life trajectories, leading to ageing phenotypes as we grow. Epigenetic mechanisms constitute the link between both external stimuli and genetic programming. Studies have focused on describing the effect of early adverse events such as trauma, famines, or childhood labor on epigenetic markers in adulthood and the elderly. However, we lack information on epigenetic programming in individuals born in rural communities from underdeveloped countries, exposed to negative influences during fetal and postnatal development, particularly chronic malnutrition. Hence, in this exploratory analysis, we characterize the epigenome of individuals and some parents from Tlaltizapan (a rural community in Mexico originally studied almost 50 years ago) and collect anthropometric data on growth and development, as well on the living conditions of the families. Our results help build a biological hypothesis indicating that most of the epigenetic age measures of the subjects are significantly different among them. Interestingly, the most affected methylated regions correspond to pathways involved in neuronal system development, reproductive behaviour, learning and memory regulation.
巴克尔假说断言，生命早期的营养不良会导致代谢重编程，从而损害生命后期的机体功能，导致与年龄相关的疾病。我们生活在会影响生命轨迹的环境和社会条件中，随着年龄的增长，会出现衰老表型。表观遗传机制是外部刺激和遗传编程之间的联系。研究集中于描述创伤、饥荒或儿童劳动等早期不良事件对成年期和老年人的表观遗传标记的影响。然而，我们缺乏关于在发展中国家农村社区出生的个体的信息，这些个体在胎儿和产后发育期间，特别是在慢性营养不良期间，会受到负面影响。因此，在这项探索性分析中，我们对来自特拉拉廷扎潘（墨西哥的一个农村社区，最初在近 50 年前进行了研究）的个体和一些父母的基因组进行了特征描述，并收集了有关生长和发育以及家庭生活条件的人体测量数据。我们的研究结果有助于构建一个生物学假说，表明研究对象的大多数表观遗传年龄测量值在他们之间存在显著差异。有趣的是，受影响最大的甲基化区域与涉及神经系统发育、生殖行为、学习和记忆调节的途径相对应。
