A comment on: Eat, fast, and live longer

A BBC Horizon programme presented by Michael Mosley. This programme explored the role of diet and nutrition in ageing.

At Cornell University researchers are studying a genetically modified mouse strain, which exhibits longevity (longer life) with a calorie restricting diet. This work has been extended to human study at Fontana Washington University. Here, they have set up a long-term study of dietary intervention. The principal investigator was quite confident that the people undertaking this approach are a new species. I doubt this very much. Participants are restricted to 1,900 calories a day, usually eaten at breakfast as a huge bowl of fruit. Time will tell if this approach does indeed lead to a longer life, but if positive results were needed, age-related tests were conducted. These included assessment of balance and reaction times, as well as blood tests for metabolic markers, and levels of body fat. Mr Mosley’s assessment was pronounced as ‘not good for his age’, but the balance and reaction time tests are both subjective and can be improved with practice. More alarming was the absolute declaration that following the calorie restriction programme for just one year will result in a reversal of disease progression. In fact, the researcher went on to say that after following the diet for 10 years, J (a volunteer) would never develop a stroke or heart attack.

The truth is that in order to fully assess the risk of death from cardiovascular disease or cancer, we would need to sequence every bit of DNA in every person in the world, follow those people from birth to death, and analyse their lifestyles for diet, exercise and environmental factors. Then, we might be able to say who will die from heart attack, or not. Some research, including my own, has identified important genes, which contribute to the risk. I have also found out that the normal variation of these genes, interacting with certain environmental factors, like stress, injury or infection, can affect the way the body responds. So, you see, it is a very complex picture, and not simply down to calorie restriction.

Professor Valter Longo, from the University of Southern California does add some science to the discussion. His research centres around an important metabolic protein, Insulin-like Growth Factor 1 (IGF1). Reduced levels of IGF1 in the blood have been associated with slowing cellular metabolism (the so called ‘go,go’ mode), increased repair of DNA damage and protection from age-related illness, in a genetically modified laboratory mouse strain.

Ex vivo research (that is, in cells taken from the animal’s body) have shown that cells in ‘go’ mode are more susceptible to cancer, as they do not show efficient cellular repair. Studies in humans have shown that calorie restriction together with a low protein diet leads to reduced circulating IGF1 levels in the blood. The mechanism of action for this is that as glucose (blood sugar) is depleted in the body, the body (in particular the large muscles) start burning fat for fuel. The liver stops or slows production of IGF1, pushing the cells into repair mode. This is not a happy state of affairs for the body of an active man or woman. Prolonged fasting can be dangerous and should only be done under medical guidance. Extreme metabolic changes can occur with short fasting protocols too. Proponents of the alternate day fast or the 5-2 fast regimes often report that they are unable to exercise on fast days due to dizziness and weakness.

The main tenet of the piece is portion control, which I endorse. It’s no secret that if you eat less and move more, your body will be stronger and healthier, provided of course that you maintain adequate nutrition. And the emergence of these fasting diets for sustained weight loss should be viewed with some skepticism.

There was no discussion about the role of our genetic make-up and ageing, or longevity. Yet, many of us will know people who live long and when asked the secret, simply say eat well, exercise a bit, and have fun.

Ethics and consent in research

In general terms, we expect that people who ask our permission, who require our consent, will have the morals and ethics to respect our wishes. Recently however, I have seen a few examples where frankly the people concerned have the morals of a snake. I’ll say no more on that, but it prompted me to think more widely about these terms; ethics, morals, consent, permission.

In my own field of life science research, no research may be undertaken without a prior favourable ethical opinion. It used be ethical approval, which implied that a peer-reviewed process had taken place, and an important group of senior people had carefully considered the application and deemed it ethical to conduct the research. Now, it simply means that a committee has spent a few minutes of the agenda discussing the merits of the work, and no responsibility or blame can be put their way should the experiment turn out not to be ethical, either in its design or in the outcomes. A matter of semantics, perhaps, but important none-the-less.

Important because many of the subjects for my research are human volunteers who trust us, the scientists, to do the right thing. Now, I don’t want to put anyone off contributing to a research project; we do still need to do research using human subjects. But I do want to point out that the administration of the rules is not what it should be. To my knowledge, there is no enforcement of the consent. I have seen inspections. I have seen paper records. I know that biological material collected years ago is still lurking in the bottom of freezers in research laboratories. Consents and research records belonging to PhD students who have long-since moved on lingering on dusty bookshelves in study rooms. There is almost no way of knowing which material should be destroyed, ethical opinion and consents having long-ago expired. And that’s just in small university laboratories. Surely in large pharmaceutical and biotech organisations the record keeping and ‘policing’ of the research consents is more robust?

Well, yes it is, and that results in a different problem. Large organisations who embark on long term research require consent from participants to be able to follow up on the outcomes of the research over a very long period of time, decades in some cases. With changes in technology, particularly in genetic research, where even five years ago the cost of this work would have prohibited it, that is no longer the case. Cost are down, through-put is up. In short, scientists can analyse more data, more quickly, at much lower costs. If the material already exists, if the methodologies are the same, there are also no start-up costs. Results could be coming within days. That means that if you volunteered ten years ago, donated a tube of your blood, approximately 10ml, and gave scientists permission to keep cells, plasma and DNA, they will still have all those bits of you in storage and on file.

I mentioned genetic research, for this is where I am most concerned. When you donated that small amount of blood all those years ago, you were probably young, in your twenties (most lab volunteers are), and too young to be showing any sign of disease. Your parents would have been young too; too young in most cases to have cancer or heart disease. You wouldn’t yet have had children either. And now, what if you are told that scientists have just worked out that your DNA shows a variation recently found to be associated with cancer – would you want to know? What would you do about it? Cancer cannot be treated if it hasn’t formed a tumour yet. This is the proposal of researchers, owners of these so-called ‘bio banks’, because original research is too expensive and largely unfunded. Would you still give your consent for your material to be used?

I believe that material collected more than five years ago should either be destroyed or re-consented. Yes, that will cost money, but it keeps science honest and transparent. It makes sure that scientists’ personal ethics and morals are not tested. It introduces a check that the material we think is there, has been stored correctly and will be useful in the research. Very often, biological material degrades over time and is useless. Better then to destroy it.

And finally, I must reveal here that I never allowed my cells or DNA to be stored. I have never used my own blood, cells or DNA in any experiment I have conducted. I do not want to know that I have a particular genetic variation. Until scientists are clever enough to re-program my genetic material, there are some things not worth knowing. Of course, there are some conditions for which there are extremely good genetic tests, and with the correct counselling, it is very helpful to do these tests. But these tests have made the transition from research to clinical application. We can’t change what has gone before, but we can make sure that we are informed about the future. Research must be done, human biological material must be used for research wherever possible. Don’t take ethics, morals, consent and permission for granted in science.

Previously published at The Camel's Hump.
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It's genetic, isn't it?

Perhaps it's time to clear something up. I get annoyed when I hear the word genetic used out of context. For example, if a homeopathic treatment does not work it is NOT because of something genetic blocking the energy. It is because the homeopathic tincture is not used at a therapeutic dose (most likely), and not because of any interaction with a gene. 

Genetics is the study of how genes are inherited in a population. A geneticist for example will be interested in the frequency of gene variation, as it relates to a human trait or characteristic.


If something is genetic, that means it is an inherited trait. Take tongue rolling. The ability to roll your tongue is a dominant trait. If you have the gene for tongue rolling you will be able to roll your tongue. Try it now. Yes? You could be homozygous (+/+ two alleles) for the gene, or heterozygous (+/- one allele). No? You are definitely homozygous (-/- two alleles) without the gene. Tongue rolling is a Mendelian genetic example. Mendelian genetics demonstrates that our genes are inherited equally from each parent. We get one allele from each gene from each parent, as shown below. 

Many inherited traits, also called phenotypes, are the result of a number of genes. This genetic make-up which includes normal gene variation, is known as the genotype. Now, some cancers are inherited, therefore it is correct to say that they have a genetic link, but in many cases cancer is a multi-factorial complex disease, being caused by more than one gene or other factor. Many cancers are not inherited but occur as a result of a spontaneous gene mutation or gene fault, most likely in response to an environmental or lifestyle factor, such as smoking. Smoking could be said to be mutagenic (affecting gene function) or carcinogenic (causing cancer). I have previously written about gene-environment interactions here.


With this simple illustration, I hope you have understood the difference between genes, genetics and mutagenic. If this bite-sized guide to genetics has whet your appetite, you will find a good reference here.

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