Genetic research has a great deal of benefit but its mysteries, such as the lack of identified genetic determinants that explain heritability of complex traits, leave a lot of biology open to speculation, like that voting for one candidate may be 'biological' or that molecular changes to our genes - epigenetic marks - are affected by what we eat.
A new paper examined the cells lining the gut wall from volunteers attending a colonoscopy clinic and determined that selenium and vitamin D status reduced the accumulation of epigenetic changes and high blood folate and obesity increased them. Healthy aging is affected by what we eat, they conclude, which is obvious. But is it really epigenetic, as in heritable changes in gene expression or cellular phenotype?
Researchers from the Institute of Food Research and Newcastle University looked at study volunteers who were free from cancer or inflammatory bowel disease and consumed their usual diet without any supplements. They looked for specific epigenetic modifications of the volunteers' genes that have been associated with the earliest signs of the onset of bowel cancer – an age-related disease. This DNA methylation does not alter the genetic code but affect whether the genes are turned on or off. The methylation marks are transmitted when cells divide, and some have been associated with the development of cancer.
The investigators studied the relationship between the occurrence of these epigenetic marks at genes known to be affected in cancer, and factors including the volunteers' age, sex, body size and the levels of some nutrients in the volunteers' blood. The biggest influence on gene methylation was age. This fits with the fact that the biggest risk factor for bowel cancer is age, with risk increasing exponentially over 50 years old.
The findings showed that men tended to have a higher frequency of these epigenetic changes than women, which is consistent with men being at a greater risk of bowel cancer. Volunteers with higher vitamin D status tended to show lower levels of methylation, and a similar effect was observed for selenium status. Again, this is consistent with the known links between higher vitamin D and selenium and reduced bowel cancer risk.
The B vitamin folate is essential for health, but in this study, high folate status was associated with increased levels of epigenetic changes linked with bowel cancer. These findings are consistent with some epidemiological studies suggesting that excessive folate intakes may increase risk in some people. The researchers intend to investigate the mechanism for the observed effect of folate on DNA methylation in a follow-up study.
Obesity is also a risk factor for bowel cancer. This study found relationships between body size (height, weight and waist circumference) and epigenetic changes. How excess body weight induces these epigenetic changes, and the consequences for gut health, are currently being investigated at IFR and in Newcastle University.
In summary, they support the hypothesis that ageing affects the epigenetic status of some genes and that these effects can be modulated by diet and body fatness.
Published in Aging Cell