Developmental Plasticity and Epigenetic Mechanisms Underpinning Metabolic and Cardiovascular Diseases

Abstract

The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

KEYWORDS::

• developmental origins of health and disease
• developmental plasticity
• epigenetics
• evolutionary medicine
• fitness
• metabolic and cardiovascular disease
• mismatch

Acknowledgements

The authors thank the many colleagues in their laboratories for stimulating discussions.

Financial & competing interests disclosure

Felicia M Low and Peter D Gluckman are supported by the National Research Centre for Growth and Development. Mark A Hanson is supported by the British Heart Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

F: Filial.

Additional information

Funding

Felicia M Low and Peter D Gluckman are supported by the National Research Centre for Growth and Development. Mark A Hanson is supported by the British Heart Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.