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A conceptual framework for the developmental origins of health and disease

Published online by Cambridge University Press:  09 December 2009

P. D. Gluckman*
Affiliation:
Liggins Institute and the National Research Centre for Growth and Development, The University of Auckland, Auckland, New Zealand Singapore Institute for Clinical Sciences, A*STAR (Agency for Science, Technology and Research), Singapore
M. A. Hanson
Affiliation:
Developmental Origins of Health and Disease Division, Institute of Developmental Sciences, University of Southampton, Southampton, UK
T. Buklijas
Affiliation:
Liggins Institute and the National Research Centre for Growth and Development, The University of Auckland, Auckland, New Zealand
*
Address for correspondence: P. D. Gluckman, Liggins Institute, The University of Auckland, Private Bag 92019, Auckland 1023, New Zealand. (Email [email protected])

Abstract

In the last decades, the developmental origins of health and disease (DOHaD) have emerged as a vigorous field combining experimental, clinical, epidemiological and public health research. Its goal is to understand how events in early life shape later morbidity risk, especially of non-communicable chronic diseases. As these diseases become the major cause of morbidity and mortality worldwide, research arising from DOHaD is likely to gain significance to public health and economic development. But action may be hindered by the lack of a firm mechanistic explanation and of a conceptual basis, especially regarding the evolutionary significance of the DOHaD phenomenon. In this article, we provide a succinct historical review of the research into the relationship between development and later disease, consider the evolutionary and developmental significance and discuss the underlying mechanisms of the DOHaD phenomenon. DOHaD should be viewed as a part of a broader biological mechanism of plasticity by which organisms, in response to cues such as nutrition or hormones, adapt their phenotype to environment. These responses may be divided into those for immediate benefit and those aimed at prediction of a future environment: disease occurs in the mismatch between predicted and realized future. The likely mechanisms that enable plasticity involve epigenetic processes, affecting the expression of genes associated with regulatory pathways. There is now evidence that epigenetic marks may be inherited and so contribute to non-genomic heritable disease risk. We end by discussing the global significance of the DOHaD phenomenon and its potential applications for public health purposes.

Type
Review
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2009

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