快猫短视频

In a back room of 快猫短视频鈥榮 offices in London, I sit down at a table with the Russian biochemist Mikhail Shchepinov. In front of us are two teaspoons and a brown glass bottle. Shchepinov opens the bottle, pours out a teaspoon of clear liquid and drinks it down. He smiles. It鈥檚 my turn.

I put a spoonful of the liquid in my mouth and swallow. It tastes slightly sweet, which is a surprise. I was expecting it to be exactly like water since that, in fact, is what it is 鈥� heavy water to be precise, chemical formula D₂O. The D stands for deuterium, an isotope of hydrogen with an atomic mass of 2 instead of 1. Deuterium is what puts the heavy in heavy water. An ice cube made out of it would sink in normal water.

My sip of heavy water is the culmination of a long journey trying to get to the bottom of a remarkable claim that Shchepinov first made around 18 months ago. He believes he has discovered an elixir of youth, a way to drink (or more likely eat) your way to a longer life. You may think that makes Shchepinov sound like a snake-oil salesman. I thought so too, but the more I found out about his idea, the more it began to make sense.

The story began two years ago, while Shchepinov was working at a biotechology company in Oxford, UK, and using his spare time to read up on the latest ideas about what causes us to age.

The most widely accepted idea is the free-radical theory. This holds that our slide into decrepitude is the result of irreversible damage to the biomolecules that make up our bodies. The main agents of this destruction are oxygen free radicals, aggressive chemical compounds that are an unavoidable by-product of metabolism.

The reason oxygen radicals are so dangerous is that they have a voracious appetite for electrons, which they rip out of anything they can lay their hands on 鈥� water, proteins, fats, DNA 鈥� leaving a trail of destruction in their wake. This damage gradually builds up over a lifetime and eventually leads the body鈥檚 basic biochemical processes to fail.

One of the worst types of damage is something called protein carbonylation, in which an oxygen radical attacks vulnerable carbon-hydrogen bonds in a protein (see diagram). This has been linked to many of the worst diseases of old age, including Parkinson鈥檚, Alzheimer鈥檚, cancer, chronic renal failure and diabetes (). Other important targets of free-radical attack are DNA and the fatty acids in cell membranes.

The human body produces legions of antioxidants, including vitamins and enzymes, that quench free radicals before they can do any harm. But over a lifetime these defence systems eventually fall victim to oxidative attack too, leading to an inevitable decline.

Many anti-ageing medications are based on supplementing the body鈥檚 own defences with antioxidant compounds such as vitamin C and beta-carotene, though there is scant evidence that this does any good (快猫短视频, 5 August 2006, p 40).

Shchepinov realised there was another way to defeat free radicals. While he was familiarising himself with research on ageing, his day job involved a well-established 鈥� if slightly obscure 鈥� bit of chemistry called the isotope effect. On Christmas day 2006, it dawned on him that putting the two together could lead to a new way of postponing the ravages of time.

The basic concept of the isotope effect is that the presence of heavy isotopes in a molecule can slow down its chemical reactions. This is because heavy isotopes form stronger covalent bonds than their lighter counterparts; for example, a carbon-deuterium bond is stronger than a carbon-hydrogen bond. While the effect applies to all heavy isotopes, including carbon-13, nitrogen-15 and oxygen-18 (see chart), it is most marked with deuterium as it is proportionally so much heavier than hydrogen. Deuterated bonds can be up to 80 times stronger than those containing hydrogen.

All of this is conventional chemistry: the isotope effect was discovered back in the 1930s and its mechanism explained in the 1940s. The effect has a long pedigree as a research tool in basic chemistry for probing the mechanisms of complex reactions.

Shchepinov, however, is the first researcher to link the effect with ageing. It dawned on him that if ageing is caused by free radicals trashing covalent bonds, and if those same bonds can be strengthened using the isotope effect, why not use it to make vulnerable biomolecules more resistant to attack? All you would have to do is judiciously place deuterium or carbon-13 in the bonds that are most vulnerable to attack, and chemistry should take care of the rest.

In early 2007 Shchepinov wrote up his idea and submitted it to a journal called Rejuvenation Research. Unbeknown to him, the journal鈥檚 editor is controversial gerontologist Aubrey de Grey of the Methuselah Foundation in Lorton, Virginia, who is well known for supporting ideas other gerontologists consider outlandish. De Grey sent the paper out for review and eventually accepted it ().

In the paper, Shchepinov points out that there is masses of existing science backing up his ideas. Dozens of experiments have proved that proteins, fatty acids and DNA can be helped to resist oxidative damage using the isotope effect.

Shchepinov鈥檚 paper brought the idea to a wider audience, including successful biotechnology entrepreneurs Charles Cantor and Robert Molinari. Impressed, they teamed up with Shchepinov to set up a company called , with de Grey as a scientific advisor.

It was around this time that I first got in touch with Shchepinov. I鈥檇 never heard of the isotope effect, and de Grey鈥檚 involvement made me cautious. But there was something in the idea that intrigued me, and I kept on coming back to it.

There were obvious objections to the idea. For one, how do you get the isotopes to exactly the sites where you want them? After all, the human body contains trillions upon trillions of chemical bonds, but relatively few are vulnerable to free-radical damage. And what about safety 鈥� swallowing mouthfuls of heavy isotopes surely can鈥檛 be good for you, can it? That, of course, is how I ended up sharing a teaspoon of heavy water with Shchepinov.

Neither, it turns out, is a big problem. Some heavy isotopes are radioactive so are obviously ruled out on safety grounds 鈥� hydrogen-3 (tritium) and carbon-14, for example. Others, notably deuterium and carbon-13, are just as stable as hydrogen and carbon-12. Both occur in small amounts in nature and are a natural component of some biomolecules in our bodies (see 鈥淗eavy babies鈥�).

Deuterium and carbon-13 also appear to be essentially non-toxic. Baby mice weaned on a highly enriched carbon-13 diet are completely normal, even when 60 per cent of the carbon atoms in their body are carbon-13. Deuterium also has a clean bill of health as long as you don鈥檛 go overboard. Decades of experiments in which animals were fed heavy water suggest that up to a fifth of the water in your body can be replaced with heavy water with no ill effects.

Similar experiments have been done on humans, albeit with lower levels of deuterium. One recent experiment kept humans on a low-level heavy-water diet for 10 weeks, during which their heavy-water levels were raised to around 2.5 per cent of body water, with no adverse effects (Biochimica et Biophysica Acta, vol 1760, p 730). The researchers also found that some deuterium became incorporated into proteins.

Heavy water, however, isn鈥檛 completely safe. In mammals, toxic effects start to kick in around the 20 per cent mark, and at 35 per cent it is lethal. This is largely down to the isotope effect itself: any protein in your body has the potential to take up deuterium atoms from heavy water, and eventually this radically alters your entire biochemistry. You鈥檇 have to drink a vast amount to suffer any ill effects 鈥� my 5 millilitres did me no harm whatsoever 鈥� but even so, Retrotope is not advocating heavy water as an elixir of youth.

Instead, it wants to package up heavy isotopes in what Shchepinov calls 鈥渋Food鈥�. This method has huge advantages, not least because it allows the heavy isotopes to be targeted to the most vulnerable carbon-hydrogen bonds. Of the 20 amino acids used by humans, 10 cannot be made by the body and must be present in the diet. That means if you supplement your diet with essential amino acids that have already had their vulnerable bonds strengthened, your body鈥檚 proteins will have these reinforced amino acids incorporated into them. Some of the building blocks of fats and DNA can also only be acquired via your diet, which means they too can be targeted using the iFood approach.

Enriched eggs

What鈥檚 more, this approach ought to be completely safe, says Shchepinov. Deuterium atoms bound to carbon in amino acids are 鈥渘on-exchangeable鈥� and so don鈥檛 leak into body water.

Another possibility is to produce meat, eggs or milk enriched with deuterium or carbon-13 by feeding deuterated water or isotope-enriched amino acids to farm animals.

For now, though, iFood remains on the drawing board as nobody manufactures the right compounds. To solve that problem, Retrotope has signed up the Institute of Bio-organic Chemistry in Moscow, Russia and Minsk State University in Belarus to make customised amino acids and fatty acids. 鈥淭here are a lot of good isotope chemists in Russia,鈥� says Cantor.

Another hurdle Retrotope will have to overcome is cost. At current prices, a litre of heavy water will set you back $300. 鈥淚sotopes are expensive,鈥� says Shchepinov. 鈥淏ut there鈥檚 no need for them to be. Methods are there to extract them, but nobody wants them.鈥� Unless demand rises, there is no incentive to produce them in bulk, and this keeps the price high.

These obstacles haven鈥檛 stopped Retrotope launching a research programme to test Shchepinov鈥檚 big idea. A team at the Institute for the Biology of Ageing in Moscow recently fed various amounts of heavy water to fruit flies to see if it had any effect on longevity. Though large amounts were deadly, smaller quantities increased lifespans by up to 30 per cent.

It鈥檚 a promising start, but it鈥檚 too early to say whether the human lifespan can also be extended in this way, or how much deuterium-enriched food you would have to eat to get a beneficial effect.

鈥淭his is preliminary and needs to be reproduced under a variety of conditions,鈥� says Shchepinov. 鈥淚t鈥檚 possible that the flies don鈥檛 like the diet, and what we鈥檙e seeing is the effects of caloric restriction [the only proven strategy for extending lifespan in experimental animals]. We need to do a lot more experiments. But still鈥︹��

Retrotope has signed up some heavyweight gerontologists to join de Grey as scientific advisors, including Jan Vijg of the Albert Einstein College Of Medicine in New York and Cynthia Kenyon of the University of California, San Francisco. Kenyon recently started work on Retrotope鈥檚 second round of experiments, giving a deuterium-enriched diet to nematode worms.

鈥淚t鈥檚 a beautiful idea,鈥� says Vijg. 鈥淚t gives us a serious chance of retarding ageing.鈥� He cautions, however, that Shchepinov鈥檚 ideas hinge on free radicals being at the root of ageing. While this is still the leading theory in the field, many researchers argue that free-radical damage alone cannot account for all the biological changes that happen as we get old ().

All of which makes other mainstream researchers very sceptical. 鈥淪hchepinov鈥檚 idea is interesting, but we鈥檙e discovering that it only makes sense to think about ageing in terms of multiple underlying causes,鈥� says Tom Kirkwood of the University of Newcastle, UK. 鈥淭he history in the field is cluttered with hypotheses which are only partially supported by the data. Therefore, it is very unlikely that his suggested mechanism will prove to be more than a small part of the much bigger picture.鈥�

Others are more positive. 鈥淚鈥檝e heard some pretty crazy ideas about how we might live longer, but I鈥檓 intrigued by this one,鈥� says Judith Campisi of the Buck Institute for Age Research in Novato, California and the Lawrence Berkeley National Laboratory, who has no formal links to Retrotope. 鈥淚t鈥檚 very original and novel.鈥�

While Retrotope is concentrating its efforts on ageing, Shchepinov says there are other applications of the isotope effect he鈥檇 like to explore. One is shielding long-term space travellers from the effects of cosmic rays and other ionising radiation, which cause damage much like ageing.

Oxidative attack on carbon-hydrogen bonds is a problem in many other areas, from drug discovery to cancer, cosmetics chemistry and electronics. If the ageing research doesn鈥檛 work out, Retrotope will try something else. 鈥淲e need to sort out what works and what doesn鈥檛, and what works well enough to be commercially exploited,鈥� says Cantor. 鈥淏ut this is going to work somewhere, because the basic science is sound.鈥�

Sound basic science, of course, doesn鈥檛 mean that Shchepinov really has cracked a problem that鈥檚 been troubling humanity for millennia. Realistically, it鈥檚 much more likely his insight will lead to a more prosaic application, such as stopping coloured plastics from fading in sunlight. But until he鈥檚 proved wrong, I鈥檒l keep on hoping that I shared my sip of heavy water with a scientist who will be remembered long after I鈥檓 forgotten.