Gluckman Peter D, Hanson Mark A, Beedle Alan S
Liggins Institute, University of Auckland, and National Research Centre for Growth and Development, Private Bag 92019, Auckland, New Zealand.
Am J Hum Biol. 2007 Jan-Feb;19(1):1-19. doi: 10.1002/ajhb.20590.
Biomedical science has little considered the relevance of life history theory and evolutionary and ecological developmental biology to clinical medicine. However, the observations that early life influences can alter later disease risk--the "developmental origins of health and disease" (DOHaD) paradigm--have led to a recognition that these perspectives can inform our understanding of human biology. We propose that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course. Such adaptive processes allow genotypic variation to be preserved through transient environmental changes. Cues for plasticity operate particularly during early development; they may affect a single organ or system, but generally they induce integrated adjustments in the mature phenotype, a process underpinned by epigenetic mechanisms and influenced by prediction of the mature environment. In mammals, an adverse intrauterine environment results in an integrated suite of responses, suggesting the involvement of a few key regulatory genes, that resets the developmental trajectory in expectation of poor postnatal conditions. Mismatch between the anticipated and the actual mature environment exposes the organism to risk of adverse consequences-the greater the mismatch, the greater the risk. For humans, prediction is inaccurate for many individuals because of changes in the postnatal environment toward energy-dense nutrition and low energy expenditure, contributing to the epidemic of chronic noncommunicable disease. This view of human disease from the perspectives of life history biology and evolutionary theory offers new approaches to prevention, diagnosis and intervention.
生物医学很少考虑生命史理论以及进化与生态发育生物学与临床医学的相关性。然而，早期生活影响可改变后期疾病风险这一观察结果——即“健康与疾病的发育起源”（DOHaD）范式——已使人们认识到这些观点有助于我们理解人类生物学。我们提出，DOHaD现象可被视为发育可塑性这一更广泛过程的一个子集，生物体通过该过程在其生命历程中适应环境。此类适应性过程使基因型变异能够通过短暂的环境变化得以保存。可塑性线索尤其在早期发育过程中起作用；它们可能影响单个器官或系统，但通常会在成熟表型中引发综合调整，这一过程由表观遗传机制支撑，并受对成熟环境的预测影响。在哺乳动物中，不利的子宫内环境会导致一系列综合反应，这表明涉及一些关键调控基因，这些基因会重新设定发育轨迹，以预期出生后条件不佳。预期成熟环境与实际成熟环境之间的不匹配会使生物体面临不良后果的风险——不匹配程度越大，风险越大。对人类而言，由于出生后环境朝着高能量密度营养和低能量消耗转变，许多人的预测不准确，这导致了慢性非传染性疾病的流行。从生命史生物学和进化理论的角度来看待人类疾病，为预防、诊断和干预提供了新方法。
