University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Level 4, Box 289, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 OQQ, UK.
Ageing Res Rev. 2017 Oct;39:96-105. doi: 10.1016/j.arr.2016.08.003. Epub 2016 Sep 1.
The prevalence of age-associated disease is increasing at a striking rate globally. It is known that a strong association exists between a suboptimal maternal and/or early-life environment and increased propensity of developing age-associated disease, including cardiovascular disease (CVD), type-2 diabetes (T2D) and obesity. The dissection of underlying molecular mechanisms to explain this phenomenon, which is known as 'developmental programming' is still emerging; however three common mechanisms have emerged in many models of developmental programming. These mechanisms are (a) changes in tissue structure, (b) epigenetic regulation and (c) accelerated cellular ageing. This review will examine the epidemiological evidence and the animal models of suboptimal maternal environments, focusing upon these molecular mechanisms and will discuss the progress being made in the development of safe and effective intervention strategies which ultimately could target those 'programmed' individuals who are known to be at-risk of age-associated disease.
全球范围内,与年龄相关的疾病的患病率正在以惊人的速度增长。众所周知,母体和/或生命早期环境不佳与发生与年龄相关的疾病(包括心血管疾病(CVD)、2 型糖尿病(T2D)和肥胖)的倾向之间存在很强的关联。为了解释这种现象,即所谓的“发育编程”,人们正在深入研究潜在的分子机制,但在许多发育编程模型中已经出现了三种常见的机制。这些机制是:(a)组织结构的变化,(b)表观遗传调控和(c)细胞衰老加速。本文综述了亚最佳母体环境的流行病学证据和动物模型,重点关注这些分子机制,并讨论了在开发安全有效的干预策略方面所取得的进展,这些策略最终可能针对那些已知存在与年龄相关的疾病风险的“编程”个体。