Epigenetic Flexibility: The Key to Reversing Chronic Disease Risk?

Flexible dynamic genetic changes, not your hard wired genetic code, may be the key to unlocking how gene-environment interactions can reverse risk of chronic diseases such as type-2 diabetes and obesity.

“Epigenetic modifications are heritable mechanisms that amend the genotype to differentially modulate the phenotype without changing the underlying DNA sequence” points out a recent review from a group at the integrative physiology research group, Karolinska Institutet, Sweden. Their focus is on how “epigenetic flexibility” could allow rapid genetic adaptions to environmental change that explain the development of chronic diseases, and also how this flexibility could be influenced by interventions such as dietary and lifestyle change.

While some epigenetic events appear to be fixed, others are highly flexible and influenced by environmental factors, like diet for example. It is this latter epigenetic flexibility that helps us adapt rapidly to environmental changes within a single generation or even our lifetime.

Historically epigenetic flexibility may have conferred an evolutionary advantage, such as a propensity for offspring to store energy more efficiency after periods of environmental stress, like famine for example. This epigenetic response to environmental stress would have conferred a survival advantage to our hunter-gatherer ancestors, but not in today’s high calorie environment.

In addition to nutrient supply environmental factors such as alcohol and tobacco consumption, environmental pollutants, and psychological stress could trigger this same historically adaptive epigenetic stress response and lead to obesity, or type 2 diabetes. “The prevalence of obesity and type 2 diabetes may then be amplified if the epigenetic shift from the offspring is passed on to further generations.”

Epigenetic responses to physical activity provide another example of epigenetic flexibility. Exercise has been shown to result in widespread, rapid and adaptive epigenetic modifications that help explain why physical activity is associated with improved metabolic function and reduced disease risk. Thus lifestyle and dietary interventions could improve health and reduce disease risk by influencing flexible epigenetic mechanisms.

“The perspective of epigenetic control is slowly evolving from the view that genomic imprints are irreversibly fixed to the notion that epigenetic DNA modifications can be rapid, reversible, and responsive to both environmental and lifestyle inputs” conclude the authors. “Because epigenetic modifications are believed to manifest both short- and long-term genetic alterations associated with metabolic diseases, global and local epigenomic marks may constitute novel targets for disease treatment and/or prevention. Lifestyle modifications such as exercise may reverse the adverse effects of epigenetic programmed metabolic disease susceptibility.”


Kirchner H, Osler ME, Krook A, Zierath JR. Epigenetic flexibility in metabolic regulation: disease cause and prevention? Trends Cell Biol. 2012 Dec 28. doi:pii: S0962-8924(12)00222-X. 10.1016/j.tcb.2012.11.008. [Epub ahead of print]

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