Chen J-H, Cottrell E C, Ozanne S E
Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Nestle Nutr Workshop Ser Pediatr Program. 2010;65:41-50; discussion 50-4. doi: 10.1159/000281144. Epub 2010 Feb 1.
Effects of in utero and early life conditions on adult health and disease such as cardiovascular disease and type 2 diabetes are well documented by epidemiological and clinical observations. Animal models including intrauterine artery ligation, maternal restriction of iron, protein or general caloric intake, provide invaluable tools to understand mechanisms linking early growth and later diseases in adult life. In addition, the rodent model of maternal protein restriction has revealed that longevity can be influenced either positively or negatively by early growth patterns. Recent rapid advances in the ageing field using model organisms involving caloric restriction and genetic mutation as well as gene overexpression demonstrated the importance of insulin/ IGF-1 signaling pathways, oxidative damage and SIRT1 in the regulation of lifespan. Studies using rodent models of maternal protein restriction suggest that alteration in insulin metabolism, changes in expression of antioxidant defense systems and in levels of oxidative damage (including telomere attrition) may also play a key role in regulation of lifespan by the early environment. It is suggested that neuroendocrine systems and epigenetic modification may be the potential mechanisms underlying beneficial or detrimental effects of early growth on the regulation of lifespan. Further studies in this area are warranted.
流行病学和临床观察充分证明了子宫内及生命早期状况对成人健康和疾病（如心血管疾病和2型糖尿病）的影响。包括子宫内动脉结扎、母体铁、蛋白质或总热量摄入受限等动物模型，为理解成年期早期生长与后期疾病之间的关联机制提供了宝贵工具。此外，母体蛋白质限制的啮齿动物模型表明，早期生长模式可对寿命产生正面或负面影响。近期在衰老领域利用涉及热量限制、基因突变以及基因过表达的模式生物取得的快速进展，证明了胰岛素/IGF-1信号通路、氧化损伤和SIRT1在寿命调节中的重要性。使用母体蛋白质限制啮齿动物模型的研究表明，胰岛素代谢改变、抗氧化防御系统表达变化以及氧化损伤水平（包括端粒磨损）的改变，也可能在早期环境对寿命的调节中起关键作用。有人提出，神经内分泌系统和表观遗传修饰可能是早期生长对寿命调节产生有益或有害影响的潜在机制。该领域需要进一步研究。
