Institute of Gerontology NAMS of Ukraine, Vyshgorodskaya st. 67, Kiev 04114, Ukraine.
Mech Ageing Dev. 2018 Jul;173:61-70. doi: 10.1016/j.mad.2018.04.003. Epub 2018 Apr 4.
Increasing evidence suggests that risk for age-related disease and longevity can be programmed early in life. In human populations, convincing evidence has been accumulated indicating that intrauterine growth restriction (IUGR) resulting in low birth weight (<2.5 kg) followed by postnatal catch-up growth is associated with various aspects of metabolic syndrome, type 2 diabetes and cardiovascular disease in adulthood. Fetal macrosomia (birth weight > 4.5 kg), by contrast, is associated with high risk of non-diabetic obesity and cancers in later life. Developmental modification of epigenetic patterns is considered to be a central mechanism in determining such developmentally programmed phenotypes. Growth hormone/insulin-like growth factor (GH/IGF) axis is likely a key driver of these processes. In this review, evidence is discussed that suggests that different aging trajectories can be realized depending on developmentally programmed life-course dynamics of IGF-1. In this hypothetical scenario, IUGR-induced deficit of IGF-1 causes "diabetic" aging trajectory associated with various metabolic disorders in adulthood, while fetal macrosomia-induced excessive levels of IGF-1 lead to "cancerous" aging trajectory. If the above reasoning is correct, then both low and high birth weights are predictors of short life expectancy, while the normal birth weight is a predictor of "normal" aging and maximum longevity.
越来越多的证据表明，与年龄相关的疾病和长寿的风险可以在生命早期被编程。在人类群体中，已经积累了令人信服的证据表明，导致低出生体重（<2.5kg）的宫内生长受限（IUGR），随后是出生后的追赶性生长，与成年后各种代谢综合征、2 型糖尿病和心血管疾病的各个方面有关。相比之下，胎儿巨大儿（出生体重>4.5kg）与非糖尿病肥胖和晚年癌症的高风险相关。表观遗传模式的发育性改变被认为是决定这种发育编程表型的核心机制。生长激素/胰岛素样生长因子（GH/IGF）轴可能是这些过程的关键驱动因素。在这篇综述中，讨论了一些证据表明，根据 IGF-1 的发育编程的生命历程动态，不同的衰老轨迹是可以实现的。在这种假设情况下，IUGR 引起的 IGF-1 缺乏导致“糖尿病”衰老轨迹，与成年后各种代谢紊乱有关，而胎儿巨大儿引起的 IGF-1 水平过高导致“癌症”衰老轨迹。如果上述推理是正确的，那么低出生体重和高出生体重都是预期寿命短的预测因子，而正常出生体重是“正常”衰老和最大寿命的预测因子。
