Mechanisms of disease: the developmental origins of disease and the role of the epigenotype
Abstract
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, and 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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People with a family history for T2DM have an increased risk for developing metabolic inflexibility; the lower HK II activity and PGC1 expression play a role in this.
“People with a family history for T2DM have an increased risk for developing metabolic inflexibility; the lower HK II activity and PGC1 expression play a role in this (136).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [136]
Perturbation of gene expression or cell proliferation and differentiation during vulnerable periods by nutritional and other environmental influences can alter the structure and functional capacity of major organ systems for life, a process known as developmental programming.
“Perturbation of gene expression or cell proliferation and differentiation during vulnerable periods by nutritional and other environmental influences can alter the structure and functional capacity of major organ systems for life, a process known as developmental programming.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [426]
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Retracted
- Authors
- Ozanne, S. E., & Constância, M.
- Affiliations
- University of Cambridge (GB)
- Babraham Institute (GB)
- Corresponding author
- Ozanne, Susan E
- Venue
- Nature Clinical Practice Endocrinology & Metabolism
- Published
- 2007-07
- Volume
- 3
- Issue
- 7
- Pages
- 539-546
- ISSN
- 1745-8366 (ISSN-L)
- 1745-8374
- OpenAlex
- W2076644905
- Cited by
- 232
- References
- 56
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 10 · 2021: 12 · 2020: 9 · 2019: 7 · 2018: 17 · 2017: 16 · 2016: 13 · 2015: 10 · 2014: 15 · 2013: 19 · 2012: 16
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Clinical Practice Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Heart Foundation
- Biotechnology and Biological Sciences Research Council (BB/D01235X/1, BB/E00797X/1, BB/D007909/1, BB/D01235X/2)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- developmental origins of health and disease, epigenotype, epigenetics, intrauterine environment, type 2 diabetes, coronary artery disease, DNA methylation, histone modifications, cellular memory, environmental programming, chronic disease, cancer
- MeSH terms
- Congenital Abnormalities, Animals, Female, Humans, Models, Biological, Pregnancy, Gene Expression Regulation, Developmental, Maternal Exposure, Epigenesis, Genetic, Embryonic Development
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