How Genetics helps Healthy Ageing

Genetic nutritioneering

It’s now clear that our genes are remarkably porous; constantly responding to changes in our environment. Diet, micronutrients, toxins, love and affection, trauma and loss can all affect them. In fact, if you could see the genes in your body as points of light as they turned on and off, you would look like a firework display.

This has huge implications for anyone trying to improve their chances of a healthy old age by changing their lifestyle. No longer is genetic engineering something confined to research labs packed with millions of dollars of high-tech equipment, it is something that you can literally do on the kitchen table. The way to change the behaviour of your genes, even some of those inherited heart-attack ones, is with a good supply of omega-3 fats, healthy levels of vitamin DWhat it does: Helps maintain strong and healthy bones by retaining calcium. Deficiency Signs: Joint pain or stiffness, backache, tooth decay, muscle cramps, hair loss…., eating a low-GL diet that keeps your blood sugar down and taking exercise.

The Methuselah worm

The gene–lifestyle link was first discovered when a top American geneticist became curious about exactly why calorieCalories are a measure of the amount of energy in food. Knowing how many calories are in the food we eat allows us to balance… restriction (CR) had such a dramatic effect not just on lifespan but on ageing healthily. Professor Cynthia Kenyon of the University of California, San Francisco, wondered if the diet could be having a direct effect on gene activity, so she cut back on the calorie intake of a number of tiny roundworms just a millimetre long, which are the genetics researcher’s ‘lab rat’.

She found that one gene in particular was turned off by the CR diet. To her big surprise, it was one that normally made more insulinInsulin is a hormone made by the pancreas. It is responsible for making the body’s cells absorb glucose (sugar) from the blood…. available. Even more of a surprise was the finding that turning the insulin gene off turned on another gene that controlled a cascade of extensive cell-repair processes. By tinkering with these genes she was able to breed some worms that lived for twice their normal 20-day lifespan.¹ With more sophisticated techniques, she’s been able to genetically engineer a strain of roundworm that lives healthily and actively for an astonishing 144 days. The human equivalent of 450 years!

Discovering this genetic mechanism opens the way to making healthy lifestyle changes in a much more focused way. It has also revolutionised ageing research, according to Jeff Holly, Professor of Clinical Sciences at Bristol University. ‘Ten years ago we thought ageing was probably the result of a slow decay, a sort of rusting,’ he says, ‘but [Cynthia Kenyon] has shown that it’s not about wear and tear but instead it is controlled by genes. That opens the possibility of slowing it down.’

Insulin – the secret ageing hormone

The key to slowing ageing could be in keeping the amount of insulin in your bloodstream down. So, all those refined sugars and carbs that you just can’t resist when you eat out could be speeding up the rate at which you are ageing. Dr Kenyon’s discoveries about what the genes in her long-lived worms were doing suggests that too much insulin is crucial in not just diabetes but in other chronic diseases as well. ‘We jokingly called the first gene the Grim Reaper,’ says Kenyon, ‘because when it’s on, which is the normal state of affairs, [the worms’] lifespan is fairly short.’

The second one had such a remarkable effect on the worms’ health that it was quickly nicknamed ‘Sweet Sixteen’, because it reduced the worms ‘age’ and turned them into teenagers. Kenyon had stumbled on a genetic Shangri la – the fictional valley where people barely aged.

Fortunately, humans have an equivalent to Sweet Sixteen (called Foxo) and turning that gene on has a number of remarkable effects. ‘Your supply of natural antioxidants goes up, damping down damaging oxidants,’ says Kenyon, ‘There’s a boost to compounds that make sure the skin and muscle building proteins are working properly, the immune system becomes more active in fighting infection and genes that are active in cancer get turned off.’

What surprised many is that the research clearly implicated insulin as being a key player in ageing and very possibly in diabetes, heart disease and cancer as well. One clear message was that keeping your insulin levels to a minimum with a low-GL diet could be a recipe for healthy ageing. High blood sugar, which triggers insulin, means the Grim Reaper stays on, and so Sweet Sixteen never gets activated.

Other ways to lower insulin release and help switch on skinny genes is to supplement chromiumWhat it does: Helps balance blood sugar, normalise hunger and reduce cravings, improves lifespan, helps protect cells, essential for heart function. Deficiency Signs: Excessive or…. The basic daily requirement for chromium, which is found in whole foods, is 50mcg, ten times this amount, 500mcg, improves insulin sensitivity, which means your body makes less, again switching on the skinny genes.² Some supplements also provide a cinnamon extract called Cinnulin, which also helps improve your metabolismMetabolism is a term that is used to describe the chemical reactions that take place within the body’s cells. The body gets the energy it….³ Specific kinds of exercises help. You need the combination of resistance training and aerobic exercise. Interval training, which involves short bursts of 30 to 60 second intense activity, such as a sprint, helps reverse insulin resistance.

The pleasures of CR without the pain

So, a low-GL diet looks like a powerful way of keeping insulin at a healthy level but, there is another way to get the benefits of CR without being condemned to a permanent state of semi-starvation. It is ridiculously simple. Eat every other day. That’s it. You fast for one day and eat as much as you like the next. Fast for another day, then eat normally and so on. Of course there are variations and guidelines. Most people eat something on the ‘down’ day, as it is called: usually between 20 and 50 per cent of the calories you’d normally have, depending on how much or how quickly you want to lose weight. And it makes sense not to binge wildly on cakes and biscuits on the normal days. I formalised this approach in my Burn Fat Fast book, which also includes specific anti-ageing exercises.

In 2003 Dr Mark Mattson, a neuroscientist at the National Institute on Ageing, discovered that rats put on the every-other-day schedule did just as well as their relatives on the gruelling CR diet.⁴ Since then, it has become a popular diet.

It has a much wider health benefit, too. A number of researchers have discovered that its effect on genes can also help with various health problems. In one small study, asthma patients lost 8 per cent of their bodyweight but they also saw a dramatic drop in levels of inflammation and damaging oxidants; symptoms of wheezing and shortness of breath both greatly improved.⁵

In another study, overweight patients dropped pounds more easily than usual and produced more of a proteinProteins are large molecules consisting of chains of amino acids. Proteins are essential nutrients for the human body – they are a building block of… called adiponectin that reduces insulin resistance (so you need less of it) and damps down inflammation.⁶ The same research team also found that getting patients to exercise, which is of course another cheap and not-patentable CR-mimetic, could produce a very similar effect.

The benefits of the Alternate Day Diet aren’t limited to reducing weight and inflammation, however. There is still a lot of research needed, but from what we have so far, how well do other schedules, such as two days eating and one day not eating, work?

It’s likely that the diet can trigger the health-promoting gene Sweet Sixteen and possibly another one called SIRT1. Some studies have found that the latter is also activated by the compound, resveratrol, found in grape skins. For this reason I supplement resveratrol every day. While a big glass of good quality red wine may provide as much as 30mg of resveratrol (organic Malbec and Merlot are best) much higher amounts of 300mg or more⁷, provided by supplements, switch on the skinny genes in the same way that calorie restriction does. Following such advice will help you age much more healthily, but there is still a lot more to be discovered.

Ageing stops when you are over 90

As an example of the mysteries of ageing that are still to be unravelled – which may be a signpost to another route to healthy ageing – take the curious fact that when you get over 90 your rate of ageing slows dramatically. Once someone passes the age of 93 they are no more at risk of dying in the following year than they are at 100.⁸ It’s been investigated by Professor Michael Rose, an evolutionary biologist at the University of California, Irvine, who has shown that the same thing happens with large populations of fruit flies. When they reach a certain point in their life span, their rate of ageing seems to plateau.

Suppose you could make that plateau effect on ageing kick in earlier, at say 70? Professor Rose suggests that when humans adopted agriculture about 10,000 years ago, some of the genes that had been valuable in hunter-gatherer groups began to cause problems in that new environment.

The major change was a large increase in foods that were based on grains and dairy products. Damaging gene reactions that kick in early in life are likely to be weeded out as the species evolves. Evolution is a numbers game: some people who are sick do reproduce, but not as many as those without the damaging gene, so on balance those with the damaging gene do less well. Rose suggests that humans are now reasonably well adapted to grains and dairy until about the age of 30, but after that they are more vulnerable to problems. So, to boost your chances of healthy ageing, he suggests that at 30-plus you adopt a more ‘Paleo’ Diet – a diet that is closer to the kind our hunter-gatherer ancestors would have been used to. Interestingly, it’s a diet that shares a key feature with the low-GL diet: it keeps blood sugar and insulin levels right down.

Vitamins that re-programme your genes

Adequate levels of micronutrients are essential for the whole complex around the genes in every cell to work effectively; for example, a team working at Oxford in the UK reported that vitamin D had a significant effect on the activity of 229 genes including some that have been associated with multiple sclerosis (MS), Crohn’s disease and type-1 diabetes.⁹

‘Our study shows quite dramatically the wide-ranging influence that vitamin D exerts over our health,’ says Dr Andreas Heger from the MRC Functional Genomics Unit at Oxford, one of the lead authors of the study. Finding out if you are deficient, and a large proportion of the population is, and then bringing yourself up to a healthy level is the kind of direct action we can all take. Another is optimising methylationMethylation is what occurs when the body takes one substance and turns it into another, so that it can be detoxified and excreted from the… by taking B vitamins.

How stress changes your genes

Staying healthy and happy as we get older involves more than keeping your mitochondria in good shape and your micronutrientMicronutrients are essentially the opposite of macronutrients. Micronutrients are still essential to good health but are only required in tiny amounts. They are commonly referred… levels up. Older people often report feelings of loneliness and lack of purpose – negative emotions that can have as direct an influence on health as biological decline. One study found that good social connections – having friends, family, neighbours or colleagues – improve our odds of survival by 50 per cent. A lack of such connections was as harmful as smoking 15 cigarettes a day and twice as harmful as obesity.¹⁰

Stress can have a large impact on our genes in ways that researchers are only just beginning to understand. Studies on rats have found that good or bad early experiences can affect the gene methylation¹¹ and that the pups of attentive rat mothers are much better able to handle stress later in life; those with less nurturing mothers become more anxious. If rat social relationships can have an effect on their genes then it’s a certainty that we intensely social humans will be directly affected too.

Stress may also increase the risk of cancer by changing genes, as scientists recently reported in Nature. Chronically stressed rats show increased DNA damage, an effect that includes turning off a gene called P53, which is known to protect against tumours. It may also affect normal brain function by causing nerve cells in the brain to make hormones and other signalling molecules they don’t normally produce.¹²

Your interconnected genes, environment, diet and state of mind

The picture that emerges from all this research is that our bodies are finely tuned ecological systems which are very sensitive to our physical, social and emotional environment. All these can directly affect the genes from birth onwards.

In summary, here’s a few simple steps you can do to re-programme your genes towards healthy ageing:

• Eat a low GL diet, keeping insulin down
• Consider alternate day fasting with two or three days a week on reduced calories or lower GL (see Burn Fat Fast)
• Avoid refined food and sugar
• Minimise wheat and milk, eating only non-gluten wholegrains infrequently
• Keep your vitamin D level up
• Supplement antioxidants including vitamin CWhat it does: Strengthens immune system – fights infections. Makes collagen, keeping bones, skin and joints firm and strong. Antioxidant, detoxifying pollutants and protecting against…, glutathione, alpha lipoic acid and resveratrol
• Keep your homocysteineHomocysteine is an amino acid found in the blood. Elevated levels of homocysteine have been associated with narrowing and hardening of the arteries, an increased… low with B vitamins to enhance methylation
• Stay physically and socially active
• Read my book The 10 Secrets of Healthy Ageing

References

1. K. Lin, et al., ‘Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling’, Nature Genetics, 2001;28(2):139–45
2. S. Anton et al., ‘Effects of chromium picolinate on food intake and satiety’, Diabetes Technology and Therapeutics , 2008 Oct;10(5):405–12
3. T. Ziegenfuss, et al., ‘Effects of a Water-Soluble Cinnamon Extract on Body Composition and Features of the Metabolic Syndrome in Pre- Diabetic Men and Women’, Journal of the International Society of Sports Nutrition , 2006; 3(2):45–53
4. R. M. Anson, et al., ‘Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake’, Proceedings of the National Academy of Sciences of the U.S.A, 2003;100(10):6216–20
5. J. B. Johnson, et al., ‘Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma’, Free Radical Biology & Medicine, 2007;42(5):665–74
6. K. A. Varady, et al., ‘Improvements in body fatThere are many different types of fats; polyunsaturated, monounsaturated, hydrogenated, saturated and trans fat. The body requires good fats (polyunsaturated and monounsaturated) in order to… distribution and circulating adiponectin by alternate-day fasting versus calorie restriction’, Journal of Nutritional Biochemistry, 2010;21(3):188)–95. Epub
7. J. Barger, et al., ‘A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice’, Public Library of Sciences ONE 2008;3(6): e2264.
8. Michael Rose, ‘Life begins at 90’, New Scientist, 2011 6 Aug
9. S. V. Ramagopalan, et al., ‘A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution’, Genome Research, 2010;20(10):1352–60
10. J. Holt-Lunstad, et al., ‘Social relationships and mortality risk: A meta-analytic review’, PLoS Medicine, 2010;7(7):e1000316
11. G. Miller, ‘Epigenetics: The seductive allure of behavioral epigenetics’, Science (New York), 2010;329(5987): 24–7
12. S. S. Gehani, et al., ‘Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation’, MolecularCell, 2010 Sep 24;39(6):886–900