Ambeskovic Mirela, Roseboom Tessa J, Metz Gerlinde A S
Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta T1K3M4, Canada.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Meibergdreef 9, University of Amsterdam, 1105 AZ Amsterdam, Netherlands; Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands.
Neurosci Biobehav Rev. 2020 Oct;117:297-316. doi: 10.1016/j.neubiorev.2017.08.002. Epub 2017 Aug 12.
Adverse early life experiences are major influences on developmental trajectories with potentially life-long consequences. Prenatal or early postnatal exposure to stress, undernutrition or environmental toxicants may reprogram brain development and increase risk of behavioural and neurological disorders later in life. Not only experience within a single lifetime, but also ancestral experience affects health trajectories and chances of successful aging. The central mechanism in transgenerational programming of a disease may be the formation of epigenetic memory. This review explores transgenerational effects of early adverse experience on health and disease incidence in older age. First, we address mechanisms of developmental and transgenerational programming of disease and inheritance. Second, we discuss experimental and clinical findings linking early environmental determinants to adverse aging trajectories in association with possible parental contributions and sex-specific effects. Third, we outline the main mechanisms of age-related functional decline and suggest potential interventions to reverse negative effects of transgenerational programming. Thus, strategies that support healthy development and successful aging should take into account the potential influences of transgenerational inheritance.
早期不良生活经历对发育轨迹有重大影响,可能产生终生后果。产前或产后早期暴露于压力、营养不良或环境毒物中,可能会使大脑发育重新编程,并增加日后出现行为和神经障碍的风险。不仅单个人一生中的经历,而且祖先的经历都会影响健康轨迹和成功衰老的几率。疾病跨代编程的核心机制可能是表观遗传记忆的形成。本综述探讨早期不良经历对老年人健康和疾病发病率的跨代影响。首先,我们阐述疾病的发育和跨代编程及遗传机制。其次,我们讨论将早期环境决定因素与不良衰老轨迹联系起来的实验和临床研究结果,并探讨可能的父母因素及性别特异性影响。第三,我们概述与年龄相关的功能衰退的主要机制,并提出逆转跨代编程负面影响的潜在干预措施。因此,支持健康发育和成功衰老的策略应考虑到跨代遗传的潜在影响。