DNA is the blueprint for you, and every cell in your body has the same exact plan. Your body uses these designs to build proteins, and proteins, in turn, do much of the work that makes you you. Knowing this, you might wonder how your organs can look so dissimilar and function so differently. After all, each of the cells in your body carries the same DNA and the same set of instructions. Recent progress in the field of epigenetics is helping us understand how this works. We now know that cells use the genetic material at their disposal in different ways but changing which genes are “expressed.” Genes are switched on and off, resulting in the extraordinary level of differentiation within our bodies.
Epigenetics describes the cellular processes that determine whether or not an individual gene transcribes and translates into its corresponding protein. The message conveys through small and reversible chemical modifications to chromatin. For example, the addition of acetyl groups (known as acetylation) to DNA scaffold proteins (histones) enhances transcription. In contrast, the addition of methyl groups (known as methylation) to some regulatory regions of the DNA itself reduces gene transcription. These modifications, together with other regulatory mechanisms, are particularly important during development – when the exact timing of gene activation is crucial to ensure proper cellular differentiation – but continue to have an effect into adulthood.
Epigenetic modifications can occur in response to your environment, one of the most important of which is diet. The mechanisms by which diet affects epigenetics are not entirely understood, but some clear examples are well known.
During the winter of 1944–1945, the Netherlands suffered a terrible famine as a result of the German occupation, and the population’s nutritional intake dropped to fewer than 1000 calories per day. Women continued to conceive and give birth during these hard times, and these children are now adults in their sixties. Recent studies have revealed that these individuals – exposed to calorie restrictions while in their mother’s uterus – have a higher rate of chronic conditions such as diabetes, cardiovascular disease, and obesity than their siblings. The first months of pregnancy seem to have had the greatest effect on disease risk.
How can something that happened before you were even born influence your life as much as 60 years later? The answer appears to lie in the epigenetic adaptations made by the fetus in response to the limited supply of nutrients. The specific epigenetic alterations are still not clear, but scientists discovered that people exposed to famine in utero have a lower degree of methylation of a gene implicated in insulin metabolism (the insulin-like growth factor II gene) than their unexposed siblings. This discovery has some startling implications: Although epigenetic changes are in theory reversible, useful changes that take place during embryonic development can nonetheless persist in adult life, even when they are no longer helpful and could even be detrimental. Some of these changes may even continue through generations, affecting the grandchildren of the exposed women.
The effects of early diet on epigenetics are also clearly visible among honeybees. What differentiates the sterile worker bees from the fertile queen are not genetics, but the diet that they follow as larvae. Larvae designated to become queens are fed exclusively with royal jelly, a substance secreted by worker bees, which switches on the gene program that results in the bee becoming fertile.
Researchers found another striking example of how nutrition influences epigenetics during development in mice. Individuals with an active agouti gene have a yellow coat and a propensity to become obese. This gene, however, can be switched off by DNA methylation. If a pregnant agouti mouse receives dietary supplements that can release methyl groups – such as folic acid or choline – the pups’ agouti genes become methylated and thus inactive. These pups still carry the agouti gene, but they lose the agouti phenotype: they have brown fur and no increased tendency towards obesity.
An insufficient uptake of folic acid causes developmental conditions in humans, such as spina bifida and other neural tube defects. Folic acid supplements are widely recommended for pregnant women and for those hoping to conceive to prevent these problems.
What about the dietary effect on epigenetics in adult life? Many components of food have the potential to cause epigenetic changes in humans. For example, broccoli and other cruciferous vegetables contain isothiocyanates, which increase acetylation. Soya, on the other hand, is a source of the isoflavone genistein, which is thought to decrease DNA methylation in particular genes. The polyphenol compound found in green tea, epigallocatechin-3-gallate, has many biological activities, including the inhibition of DNA methylation. Curcumin, a compound found in turmeric, can have multiple effects on gene activation because it inhibits DNA methylation but also modulates acetylation.
Most of the data collected so far about these compounds come from in vitro experiments. It is unknown if eating the corresponding foods has the same detectable effect as has been seen.
Epidemiological studies suggest that populations that consume large amounts of some of these foods appear to be less prone to certain diseases. However, most of these compounds have not only epigenetic effects but affect other biological functions as well. A food source may contain many different biologically active molecules, making it difficult to draw a direct correlation between epigenetic activity and the overall effect on the body. Finally, all foods undergo many transformations in our digestive system, so it is not clear how much of the active compounds reach their molecular targets.
As a result of their far-reaching effects, epigenetic changes may aid in the development of many illnesses, including some cancers and neurological diseases. As cells become malignant, or cancerous, epigenetic modifications can deactivate tumor suppressor genes, which prevent excessive cell proliferation. Because these epigenetic modifications are reversible, there is keen interest in finding molecules – especially dietary sources – that might undo these damaging changes and prevent the development of the tumor.
We all know that a diet rich in fruit and vegetables is healthy for our everyday life, but it is becoming increasingly clear that it might be much more important than that, having significant implications for our long-term health and longevity.
There is a fairly common belief that we need to eat healthy to lose weight, and exercise to live longer. While this is truer than the notion that exercise will help you lose weight, scientists are starting to discover that diet has more to do with prolonging your life than we first thought. It can even change your DNA. The very stuff that makes you you.