Re: iFood, Heavy Water and Ageing

[Guest guest]

Yes, very interesting. I saw a documentary recently where they were

talking about hard water in certain areas being the cause of so called

'blue zone', with a disproportionate amount of centarians living in

these areas. The supposition is that the hard water (particularly the

calcium and magnesium), combined with good levels of Vitamin D from

the sun, provides the longevity.

On Thu, Nov 27, 2008 at 4:53 PM, alistair tweed

<tumble23_2000@...> wrote:

> Would eating heavy atoms lengthen our lives?

> * 27 November 2008 by Graham Lawton

>

> In a back room of New Scientist's 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's 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 - 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 - water, proteins, fats, DNA - leaving a trail of

> destruction in their wake. This damage gradually builds up over a

> lifetime and eventually leads the body's 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's, Alzheimer's, cancer, chronic renal failure and diabetes (The

> EMBO Journal, vol 24, p 1311). 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's own

> defences with antioxidant compounds such as vitamin C and

> beta-carotene, though there is scant evidence that this does any good (New

> Scientist, 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 - if slightly obscure - 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's 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 (Rejuvenation Research, vol 10, p 47).

> 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's

> paper brought the idea to a wider audience, including successful

> biotechnology entrepreneurs Cantor and Molinari.

> Impressed, they teamed up with Shchepinov to set up a company called

> Retrotope, with de Grey as a scientific advisor.

> It

> was around this time that I first got in touch with Shchepinov. I'd

> never heard of the isotope effect, and de Grey's 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 - swallowing mouthfuls of heavy isotopes surely can't 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 - 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 " Heavy babies " ).

> 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't 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't 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'd have to drink a vast amount to suffer any ill effects - my 5

> millilitres did me no harm whatsoever - 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 " iFood " .

> 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's 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's

> more, this approach ought to be completely safe, says Shchepinov.

> Deuterium atoms bound to carbon in amino acids are " non-exchangeable "

> and so don't 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..

> " There are a lot of good isotope chemists in Russia, " says Cantor.

> Another

> hurdle Retrotope will have to overcome is cost. At current prices, a

> litre of heavy water will set you back $300. " Isotopes are expensive, "

> says Shchepinov. " But there's no need for them to be. Methods are there

> to extract them, but nobody wants them. " Unless demand rises, there is

> no incentive to produce them in bulk, and this keeps the price high.

> These

> obstacles haven't stopped Retrotope launching a research programme to

> test Shchepinov's 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's

> a promising start, but it's 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.

> " This

> is preliminary and needs to be reproduced under a variety of

> conditions, " says Shchepinov. " It's possible that the flies don't like

> the diet, and what we're 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... "

> 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 Kenyon of the University of

> California, San Francisco. Kenyon recently started work on Retrotope's

> second round of experiments, giving a deuterium-enriched diet to

> nematode worms.

> " It's

> a beautiful idea, " says Vijg. " It gives us a serious chance of

> retarding ageing. " He cautions, however, that Shchepinov's 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 (Nature, vol 451, p 644).

> All

> of which makes other mainstream researchers very sceptical.

> " Shchepinov's idea is interesting, but we're discovering that it only

> makes sense to think about ageing in terms of multiple underlying

> causes, " says Tom Kirkwood of the University of Newcastle, UK. " The

> 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. "

> Others

> are more positive. " I've heard some pretty crazy ideas about how we

> might live longer, but I'm intrigued by this one, " 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. " It's very original and novel. "

> While

> Retrotope is concentrating its efforts on ageing, Shchepinov says there

> are other applications of the isotope effect he'd 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't work out, Retrotope will try something else.

> " We need to sort out what works and what doesn't, and what works well

> enough to be commercially exploited, " says Cantor. " But this is going

> to work somewhere, because the basic science is sound. "

> Sound

> basic science, of course, doesn't mean that Shchepinov really has

> cracked a problem that's been troubling humanity for millennia.

> Realistically, it's much more likely his insight will lead to a more

> prosaic application, such as stopping coloured plastics from fading in

> sunlight. But until he's proved wrong, I'll keep on hoping that I

> shared my sip of heavy water with a scientist who will be remembered

> long after I'm forgotten.

> Heavy babies

> The

> idea of using chemical isotopes to combat ageing may be new, but nature

> may already be onto that strategy as a way of protecting us against

> free-radical attack, thought to be a key cause of ageing. Babies and

> mice are born with much more of the isotope carbon-13 in their bodies

> than their mothers, and women appear to become unusually depleted in

> carbon-13 around the time they give birth. Both findings suggest that

> there is active transfer of carbon-13 from mother to fetus.One possible

> reason for this, suggests Mikhail Shchepinov, chief scientific officer

> of the biotechnology company Retrotope, which is investigating the use

> of isotopes to slow ageing, is that the growing fetus selectively

> builds carbon-13 into its proteins, DNA and other biomolecules to take

> advantage of the way that heavy isotopes make these molecules more

> resistant to free-radical attack.It would make good evolutionary sense,

> as many of the proteins and DNA molecules formed early on have to last a

> lifetime.

> " Every single atom in the DNA of the brain of a 100-year-old man is the

> same atom as when he was 15 years old, " says Shchepinov (BioEssays, vol 29,

> p 1247).

> http://aging-management.com/ - Optimising Health for Longevity

>

>

[Guest guest]

Hi,

One needs more study.

Heavy water seems to be toxic.

Google " Heavy water toxic " for more info.

================================

Hamish wrote:

> Yes, very interesting. I saw a documentary recently where they were

> talking about hard water in certain areas being the cause of so called

> 'blue zone', with a disproportionate amount of centarians living in

> these areas. The supposition is that the hard water (particularly the

> calcium and magnesium), combined with good levels of Vitamin D from

> the sun, provides the longevity.