The dogma that genes determine destiny has been substantially revised by the science of epigenetics. Your genome, the sequence of DNA in each cell, is largely fixed from conception. But how that genome is expressed, which genes are switched on or off, at what level, and in which tissues, is dynamically regulated by epigenetic mechanisms: DNA methylation, histone modification, and non-coding RNA expression. These epigenetic marks are influenced by almost every aspect of the environment, and among the most powerful environmental regulators of epigenetic marks is food. What you eat, when you eat it, and how much of it you eat, all change gene expression in ways that are measurable within hours and can accumulate over a lifetime.
Methyl Groups and DNA Methylation
DNA methylation, the addition of a methyl group to a cytosine base in the DNA sequence, is one of the primary mechanisms by which genes are silenced. When genes are methylated in their promoter regions, the transcriptional machinery cannot access them and they are switched off. The methyl groups used in DNA methylation come directly from dietary methyl donors: folate, vitamin B12, betaine from beets and spinach, and choline from eggs and liver. A diet deficient in these nutrients reduces the capacity to maintain DNA methylation patterns, with consequences that include the activation of genes that should be silenced, including some oncogenes. A diet rich in these methyl donors supports the maintenance of appropriate gene silencing.
Polyphenols as Epigenetic Regulators
Plant polyphenols are increasingly understood to function as epigenetic regulators rather than simply antioxidants. Curcumin from turmeric inhibits DNA methyltransferases and histone deacetylases, enzymes that modify epigenetic marks in cancer-relevant genes. EGCG from green tea inhibits DNA methyltransferase activity, potentially reversing the hypermethylation of tumour suppressor genes. Resveratrol activates sirtuins, the NAD+-dependent histone deacetylases that regulate chromatin structure and are implicated in longevity. These epigenetic effects occur at dietary doses and provide a mechanistic explanation for the epidemiological associations between polyphenol-rich diets and reduced cancer incidence.
The mTOR and AMPK Nutrient Sensing Pathways
Two master nutrient-sensing pathways, mTOR and AMPK, translate the nutritional state of the cell into gene expression changes. mTOR, activated by amino acids and growth factors, drives the expression of anabolic programmes: protein synthesis, cell growth, and proliferation. AMPK, activated by a low energy state, drives catabolic programmes: fat oxidation, autophagy, mitochondrial biogenesis, and the expression of stress resistance genes. Dietary patterns that maintain mTOR and AMPK in appropriate balance, typically achieved by time-restricted eating, adequate but not excessive protein, and regular vigorous exercise, are associated with the gene expression profiles of biological youth. Chronic mTOR overactivation through constant eating and caloric excess is associated with accelerated ageing.
Food Compounds With the Strongest Epigenetic Evidence
- Sulforaphane from broccoli: activates Nrf2, the master antioxidant transcription factor, switching on hundreds of cytoprotective genes; also inhibits HDAC enzymes to reverse epigenetic silencing of tumour suppressor genes; a clinical trial found measurable NRF2 pathway activation in humans after broccoli sprout extract consumption
- Folate from dark leafy greens: directly provides methyl groups for DNA methylation maintenance; deficiency in pregnancy is the most established nutritional epigenetic insult, producing neural tube defects through hypomethylation
- Omega-3 fats: alter the fatty acid composition of cell membranes, affecting receptor distribution and signalling dynamics, and directly modulate the expression of inflammatory genes through nuclear receptor activation
- Resveratrol: activates SIRT1 at supradietetary doses; at dietary doses from red wine and grapes, resveratrol's contribution is modest but combined with other polyphenols in a Mediterranean diet the sirtuin pathway effects are measurable
- Caloric restriction: the most robust epigenetic intervention in animal models; reduction in mTOR activity and increase in AMPK activity reverses hundreds of age-associated gene expression changes; in humans, the most practical equivalent is time-restricted eating and avoidance of chronic caloric excess
Sources
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- Park, L.K., et al. (2012). Dietary methyl donor restriction alters murine DNA methylation. FASEB Journal, 26(2), 827-838.
- Mazzio, E.A., & Soliman, K.F. (2012). Epigenetics and nutritional environmental signals. Integrative and Comparative Biology, 52(3), 439-453.