Good for your age: Epigenetic Effects on the aging process

DNA ReplicationAre high folic acid levels healthy as we age. Epigenetics is a relatively new strand of genetic science.

Its range of action relating to the aging process is becoming apparent and its role in higher than average risk of bowel cancer is clearer. It describes the search for answers about why we first thought that the human genome contained a lot of “junk” DNA. Well it does not. More and more research is pointing up the importance of signals and how the previously described “junk” DNA encodes for this within the gene itself.

At its core, the basis of DNA and RNA function and interaction involves signals and signalling. Another way of visualising the function of the epigenome is to imagine the DNA as a train network and the epigenome as the signalling system that sets the signals so that the points open and close and the gene does not suffer a crash.

Another way of thinking about epigenetics is that the DNA contained in genes is somewhat like an orchestra. For music to occur, not every instrument plays all the time. For large chunks of the classics, certain sections remain silent for long periods. Do we think of them as ‘junk’? For music to be proficient, the orchestra, helped by the conductor have to keep certain rules of timing and harmony. An orchestra with no conductor is in trouble.

The next bit of news to tickle my fancy this week concerns an article about epigenetics and diet for healthy aging. Again, it is from, which I have to say is a favourite of mine. I have posted the article in full, as its findings on diet are significant, in that it has shown how increased folate levels may increase the risk of bowel cancer in some people, through its interaction with the epigenome.

SO TOO MUCH is not always good for you. That we have known for eons. The twist now is that we may have to alter the balance of our diet as we age, to reduce risk, and increase benefit.

The article summarised the study’s findings thus.

The bold sections are my own emphasis.

“Researchers from the Institute of Food Research led by Dr Nigel Belshaw, working with Prof John Mathers and colleagues from Newcastle University, examined the cells lining the gut wall from volunteers attending colonoscopy clinic. The Institute of Food Research is strategically funded the Biotechnology and Biological Sciences Research Council and this study was also funded by the Food Standards Agency.

The study volunteers were free from cancer or inflammatory bowel disease and consumed their usual diet without any supplements. The researchers 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. These epigenetic marks, known as DNA methylation, do not alter the genetic code but affect whether the genes are turned on or off. These 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, published in the journal Aging Cell, showed that men tended to have a higher frequency of these epigenetic changes than women did, 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 results of this study showing an association between folate status and epigenetic changes linked to cancer, together with those from another recent study by Nigel Belshaw’s group showing that, in cells grown in the laboratory, they could be induced by exposure to high levels of folic acid, emphasise the need for further research on optimal folate status in humans. The researchers intend to investigate the mechanism for the 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, the results of this study support the hypothesis that aging affects the epigenetic status of some genes and that these effects can be modulated by diet and body fatness.”


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