Date

January 20, 2014

Divergence: Sue Parsons and Rose Cushing of Upper Caboolture, Queensland, are identical twins who have developed different health profiles, despite having the same upbringing.

It’s the time of year when New Year’s resolutions are still in our awareness, and you wonder whether you should make plans to lose weight, get fit or eat better. If the whole concept is losing its shine, here’s one phenomenon that could radically reinvigorate your resolve to get healthy and – guess what? – that reason isn’t all about you, but about your children and your grandchildren.

The disturbing proposition is that you won’t be taking your hard-partying or slothful ways to the grave. No, they can live on and be passed down to future generations.

At least that is the possibility being presented by the study of epigenetics, which shows that we are connected to our ancestors in ways once thought impossible.

Long game: Professor Tim Spector researches how seemingly subtle influences can affect health in the long term. Photo: Tamara Dean

Consider this: if your biological father smoked, but you were adopted from birth and never saw or lived with him, could your health be damaged? That might sound like a Zen koan, a paradoxical question to be meditated upon, but it’s not.

However, the answer, which is yes, is just as mind altering.

Epigenetics takes place where nature meets nurture, where the environment interacts with our genes, creating a new type of soft inheritance, a kind of short-lived adaptation to our life circumstances.

It involves turning genes on or off, so the genes themselves remain the same, but are turned up or down by chemical switches that sit above the genes, controlling gene expression. The effect could be better or worse health, depending on which genes are affected and how. Environmental stimuli, such as diet, stress or pollutants, seem capable of flicking these switches.

The amazing bit is that sometimes these switches are passed down to future generations, even when the trigger is removed.

For example, pregnant rats given nicotine produced asthmatic pups that went on to produce their own asthmatic pups, despite the absence of nicotine exposure in the third generation, according to a study conducted by the Los Angeles Biomedical Research Institute, published last year.

Conducting these types of experiments in humans isn’t possible for ethical reasons.

That is why epigeneticist Professor Tim Spector is scouring the world for identical twins, who provide a perfect model for studying epigenetics.

Spector, who is director of the Department of Twin Research and Genetic Epidemiology at St Thomas’ Hospital, London, visited Australia late last year promoting his new book, Identically Different – Why You Can Change Your Genes.

Identical twins might look the same, talk the same and have similar mannerisms, but scratch the surface and there can be more differences than similarities, says Spector, especially when it comes to health.

”As a rheumatologist, I became very interested in the fact that when one twin developed rheumatoid arthritis, the other rarely did,” he says.

”When we looked at identical female twins with the disease, 85 per cent of the women never developed their sister’s disease.”

On further investigation, he found that, for most diseases studied, there was rarely more than a 50 per cent chance of both twins getting the same disease. The reason for such disparity is the epigenetic differences between them, he says.

Sue Parsons and Rose Cushing, of Upper Caboolture, Queensland, are identical twins who have developed markedly different health profiles, despite sharing the same upbringing. They lived with their parents until the age of five, when the marriage failed, then with foster parents, followed by life in an orphanage from the age of seven to 17, when both trained to become nurses. Now aged 63, they work in the same hospital.

”We are so close. Even what we eat and the fruits we prefer are the same,” says Sue. ”When we were younger, Rose smoked for a bit longer than me before we gave up and perhaps drank a little more, but otherwise our lifestyle has been very similar.”

Ten years ago, Sue developed bowel cancer, which spread to her liver, resulting in the removal of 60 per cent of her liver and part of her colon. Sue also has ankylosing spondylitis, which has a strong genetic component. But Rose has neither of these conditions.

These kinds of twins are ”like gold dust”, Spector says, because they allow researchers to investigate what might be causing the differences in health outcomes, other than genes or environment. It can’t be because of a difference in genes, since identical twins are genetic clones of each other, and it’s unlikely to be because of differences in lifestyle or environment, since twins are usually raised the same way and often go on to choose similar life paths.

With a strong history of cancer in their biological family, it is no surprise that Sue and Rose might have inherited some cancer genes. Their mother died of lung cancer from smoking, their father had prostate cancer. Their grandmother died of breast cancer and a great-grandmother had rheumatoid arthritis.

But why is only one twin affected? And if the difference between the two is explained by epigenetics – certain genes being switched on or off – what caused that, given a very similar upbringing and lifestyle?

”Both twins could have inherited cancer genes as well as the epigenetic changes induced by smoking,” says Spector. ”But in one, the bad susceptibility gene could have been switched off. The reason for that could have been luck. Certain parts of us are programmed to be unpredictable.

”It could be something in the environment that we don’t know about yet, such as exposure to some kind of pollutant, or Sue and Rose could have had quite different experiences in their mother’s womb. One twin is often more squashed than the other, and one tends to get more nourishment. Such early differences could have major effects on gene expression later in life.

”In the case of ankylosing spondylitis, we think that a viral infection can activate the related genes, so if Sue caught a virus and Rose didn’t, that may explain the difference,” says Spector.

Epigenetic control isn’t a completely new concept. It’s needed for us all to develop normally, to silence or activate various genes to allow different cells, tissues and organs to be created from the same genetic material contained in every cell. It’s the discovery of the heritability of epigenetic changes, even when the environmental trigger is absent, that is attracting attention.

It is early days in human research, but some studies indicate that factors such as famine, stress and smoking can affect the third generation.

For example, women who were pregnant during the Dutch famine in the winter of 1944-45 had children who were more prone to diabetes, a trait that was also more common in their grandchildren, says Spector. The Avon Longitudinal Study of Parents and Children found that boys of grandfathers who smoked early in life were more likely to be obese. It is believed that epigenetic changes triggered by smoking alter the metabolic state in some way in the next generations.

It’s the kind of result that brings to mind the biblical curse: ”The sins of the fathers will be visited on the children, even unto the third and fourth generations”.

These kinds of observations have some wondering whether current common afflictions such as obesity and diabetes, which don’t seem to be completely explained by genes or the environment, have their root cause in earlier generations.

Meanwhile, what does it all mean for the average person? It’s enough to make your head spin, and your moral compass swing between guilt, blame and a heightened sense of responsibility.

If you are feeling guilty about what you might have passed onto your children, it may offer small comfort to know that most of your genes become all squeaky clean again when they are in the process of forming into a new baby.

You may now feel justified in blaming your parents for handicapping your health if their lifestyle set your genetic switches in an unfavourable manner. Fair enough, but that is something you won’t know for sure, and blame has a limited shelf life once you become an adult.

”Irrespective of the cards you’ve been dealt by your parents, the epigenetic effect is small compared with the lifestyle you can choose now,” contends molecular geneticist Professor Merlin Crossley, of the University of Sydney.

As for parents to be: ”It really does matter what you do to your body,” Spector concludes in his book.

”Your grandparents may have faced stressful events like famine and war that couldn’t be avoided, but you might face choices like quitting smoking or improving your diet. These can influence your life and several generations more.”

What is epigenetics?

Epigenetics is the study of how chemical changes caused by our environment can change the way our genes work, without altering DNA structure. DNA is a stable molecule found in every cell that contains all our genetic information.

How does it work?

One of the most easily studied chemical changes or switches that regulates gene expression is a process called methylation, where methyl groups – chemical structures composed of one carbon atom and three hydrogens – attach themselves to the DNA itself, or to proteins that coat the DNA, called histones.

Methylation usually leads to silencing a gene, whereas under-methylation can lead to uncontrolled expression.

Twin Registry

Twins who want to help researchers better understand the effect of genetic and environmental factors on health and disease can sign up with the Australian Twin Registry: twins.org.au

If you had your time with an epigeneticist, what would you ask?

N.B. Qualify each answer with: “It’s very early days and most of the research has been done on mice.”

1. What environmental toxins or lifestyle choices are capable of flicking our gene switches?

Examples in animals: stress or abuse, alcohol, lack or overuse of essential vitamins, high-fat diets, overeating, drugs such as cocaine and nicotine, inorganic contaminants such as arsenic, chemicals used as fungicides or pesticides such as DDT and bisphenol A (BPA) in plastics.

Examples in humans: early smoking, famine. More answers will soon be available from current international and national longitudinal studies that are following babies from birth and tracking how DNA in their blood changes according to various lifestyle factors.

2. Does exposure to an insult (eg stress, pollutant) in the parent affect all children or grandchildren?

“The effect is patchy and not predictable,” says Professor Tim Spector. “So if you have a litter of 10, half of these might be affected and the other half not.”

3. How many generations do epigenetic changes last, when the trigger is no longer there?

In humans they have been observed in the third generation, in rodents in the fifth generation and in plants they can last up to 10 generations.

4. Are epigenetic changes reversible?

Yes. This naturally happens during the very early stages of embryo development; 95 to 99 per cent of the signals or switches passed down from your parents are wiped clean. A few signals escape the cleaning process for unknown reasons.

5. Can I reverse epigenetic changes for the better through changing my lifestyle?

“If you stop smoking, within three months you can reverse the epigenetic changes caused by smoking,” says Spector. “And exercising three times a week has been shown to turn down a specific obesity gene.”

Epigenetics could be thought of as a quicker type of adaptation than evolution, one that allows you to revert if the change in environment is only temporary.

Sources: Professors Tim Spector, Margaret Morris, (UNSW), Merlin Crossley (UNSW), Susan Clark (Garvan Institute).