Szyf Moshe
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Biochim Biophys Acta. 2009 Sep;1790(9):878-85. doi: 10.1016/j.bbagen.2009.01.009. Epub 2009 Feb 3.
Several lines of evidence point to the early origin of adult onset disease. A key question is: what are the mechanisms that mediate the effects of the early environment on our health? Another important question is: what is the impact of the environment during adulthood and how reversible are the effects of early life later in life? The genome is programmed by the epigenome, which is comprised of chromatin, a covalent modification of DNA by methylation and noncoding RNAs. The epigenome is sculpted during gestation, resulting in the diversity of gene expression programs in the distinct cell types of the organism. Recent data suggest that epigenetic programming of gene expression profiles is sensitive to the early-life environment and that both the chemical and social environment early in life could affect the manner by which the genome is programmed by the epigenome. We propose that epigenetic alterations early in life can have a life-long lasting impact on gene expression and thus on the phenotype, including susceptibility to disease. We will discuss data from animal models as well as recent data from human studies supporting the hypothesis that early life social-adversity leaves its marks on our epigenome and affects stress responsivity, health, and mental health later in life.
多条证据指向成年期发病的早期起源。一个关键问题是：介导早期环境对我们健康产生影响的机制是什么？另一个重要问题是：成年期环境有何影响，以及早期生活的影响在生命后期的可逆程度如何？基因组由表观基因组编程，表观基因组由染色质组成，染色质是通过甲基化和非编码RNA对DNA进行的共价修饰。表观基因组在妊娠期间形成，导致生物体不同细胞类型中基因表达程序的多样性。最近的数据表明，基因表达谱的表观遗传编程对早期生活环境敏感，生命早期的化学和社会环境都可能影响表观基因组对基因组进行编程的方式。我们提出，生命早期的表观遗传改变可能对基因表达产生终身持久影响，从而对包括疾病易感性在内的表型产生影响。我们将讨论来自动物模型的数据以及来自人类研究的最新数据，这些数据支持这样的假设，即生命早期的社会逆境会在我们的表观基因组上留下印记，并影响生命后期的应激反应、健康和心理健康。
