期刊
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM
卷 3, 期 7, 页码 539-546出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncpendmet0531
关键词
birth weight; diabetes; epigenetics; nutrition; programming
资金
- Biotechnology and Biological Sciences Research Council [BB/E00797X/1, BB/D01235X/1, BB/D007909/1, BB/D01235X/2] Funding Source: researchfish
- Medical Research Council [G0600717B] Funding Source: researchfish
- BBSRC [BB/D007909/1, BB/D01235X/1, BB/D01235X/2, BB/E00797X/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D01235X/1, BB/D01235X/2, BB/D007909/1, BB/E00797X/1] Funding Source: Medline
There is accumulating evidence that many chronic diseases such as type 2 diabetes and coronary heart disease might originate during early life. This evidence gives rise to the developmental origins of disease hypothesis, an is supported by epidemiological data in humans and experimental animal models. A perturbed environment in early life is thought to elicit a range of physiological and cellular adaptive responses in key organ systems. These adaptive changes result in permanent alterations and might lead to pathology in later life. Aging organs and cells seem therefore to retain a 'memory' of their fetal history and adaptive responses. The mechanisms underlying the developmental origins of disease remain poorly defined. Epigenetic tagging of genes, such as DNA methylation and histone modification, controls the function of the genome at different levels and maintains cellular memory after many cellular divisions; importantly, tagging can be modulated by the environment and is involved in onset of diseases such as cancer. Here we review the evidence for the developmental origins of disease and discuss the role of the epigenotype as a contributing mechanism. Environmentally induced changes in the epigenotype might be key primary events in the developmental origins of disease, with important clinical implications.
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