Bolstering cells with a dose of heavy fat may be the key to curing degenerative diseases. And it may help you hold back the years

Holding back the years (Image: Image Source/plainpicture)

COULD a shiny orange capsule of modified fat help to keep you young? For the first time next month, fats designed to reinforce our cells against age-related damage will be given to people in a clinical trial. The participants have a rare genetic disorder, but if the treatment works for them, it could eventually help us all live longer, more youthful lives, says the scientist behind the work.

Mikhail Shchepinov, director of Retrotope, a biotech company based in Los Altos, California, wants eventually to slow down the ageing process. But he is starting with a related problem – treating the inherited movement disorder Friedreich’s ataxia, with which ageing shares a mechanism. They are both caused, in part, by a molecular attack on our cells. Shchepinov’s idea is to counteract this assault by reinforcing our cells’ defences, slowing the progression of this incurable disease. If it works, it should demonstrate that the approach is also suitable for tackling ageing.

The damage he wants to address is caused by molecules called oxygen free radicals, made when our cells metabolise. Free radicals have unpaired electrons that desperately try to find a partner by tearing electrons off other molecules. This triggers a chain reaction as the denuded atom then does the same to its neighbour.


This chain reaction is particularly dangerous for the fatty acids that form our cell membranes. “They burn like gunpowder until hundreds of thousands are damaged,” says Shchepinov. Proteins and DNA also come off badly. Blocking the reaction should prevent the damage, but Shchepinov has a different idea.

He reckons we can protect our cells from free radicals simply by strengthening the bonds between molecules that make up our cell membranes. This can be done by swapping the hydrogen in the fatty acids for a different form known as deuterium. Because deuterium has an extra neutron, it is heavier than hydrogen and forms stronger bonds (see “The skinny on heavy fat“).

“Swapping some of the fat we eat with stronger fats should allow us to build more robust cells”

Enter the modified fat pill. The idea is that substituting some of the fats we normally eat with modified, stronger fats in pill-form should allow us to build stronger cells. To test the idea, Shchepinov and his colleagues developed heavy versions of an omega-6, polyunsaturated fatty acid. “It’s not a nutrient – it’s a new chemical that is different from the fats you get in your diet,” says Retrotope co-founder Robert Molinari, the biochemist who is leading the clinical trial.

The approach works in yeast – samples that metabolised heavy fats appear to be up to 150 times as resistant to the oxidative stress caused by free radicals as those given regular fatty acids.

The next step is to see whether heavy fat can slow the progression of Friedreich’s ataxia. This is caused by free radical damage to the nerves responsible for movement and usually means people are wheelchair-bound within 10 to 20 years of symptoms appearing. The idea makes sense, says Corinne Spickett at Aston University in Birmingham, UK. “The underlying chemistry is quite correct – the fats are theoretically less susceptible to attack by free radicals,” she says.

The trial launching in June is a safety study. The team will be checking that the doses of heavy fat are well tolerated by 18 people with Friedreich’s ataxia. They don’t expect problems – even if every cell membrane were made from their modified fatty acids, the total amount of deuterium in the body would still be around four times lower than a dangerous dose.

At first, each volunteer will be given two 1 gram tablets of heavy fat per day. “It looks like a fish oil pill,” says Molinari. After a break, the dose will be ramped up, with people taking five tablets, twice a day. Because the heavy fats need to overwhelm the fats we usually get in our food, the volunteers will be placed on a special diet. “They can have olive oil and saturated fats but not polyunsaturated fatty acids,” says Shchepinov.

Reverse the damage

Molinari hopes that the treatment will not only halt the progression of the disease, but also improve people’s symptoms. By replacing cellular fatty acids with stronger ones, there is a chance of rescuing nerves that are sick, but not dead. “A degree of reversal of damage is possible,” he says. “We see improvements in cell experiments – we won’t know about the effects in people until we do the trial.” Although a larger trial will be needed to determine any effect on symptoms, the team is hoping to see some hints during the safety study.

“The principle is sound, and some beneficial effects of heavy fats have been seen in cells and rodents,” says Spickett. “But will this translate to humans? We’ll have to see.”

Theoretically, heavy fats could also prove useful in other diseases in which free radicals are implicated, such as Parkinson’s. A few years ago, Shchepinov and colleagues at the University of Arkansas and the Scripps Research Institute in California, found that a diet rich in heavy fats protected mice against the worst ravages of the mouse equivalent of Parkinson’s disease.

And then there’s the question of whether a heavy fat pill can slow ageing. “If you can fix oxidative damage then lifespan will be extended,” says Shchepinov. “It’s the same mechanism.”

To get a better idea of its potential, the team plans to run a trial in rodents, lasting around three years. A human trial would be more complicated as it would be incredibly difficult to tease apart the many factors known to play a role in ageing (see “Ageing explained“). “The jury is still out on the free radical theory of ageing,” says Mark Cooper at University College London. “Free radicals do contribute to ageing, but there is a massive amount going on – it might not just be down to one thing.”

“Free radicals contribute to ageing, but there is so much going on, it might not just be down to this”

But Shchepinov is sanguine. To him, ageing is just a collection of diseases. If the fatty acids benefit people with these diseases, they will automatically extend lifespan, he says. “Maybe people will live until they are 180 and start dying of something else,” he says. “It’s a complex approach, but I hope our fatty acids will play a role.”

Ageing explained You’re born, you age, you die. But no one is exactly sure what’s going on under the hood. Here are some ideas about why we age: Blame the free radicals When cells metabolise they produce reactive molecules called free radicals that attack other molecules, harming cells in the process. The damage is known as oxidative stress and as it accumulates over time, it is thought to cause the general wear and tear of the body as we age. Chromosomes worn away The ends of our chromosomes are capped with bundles of protective DNA called telomeres. These shrink every time a cell divides, until eventually, the telomeres are too short for this to happen. When cell division stops, the cells are unable to replenish themselves and maintain the body’s tissues, leading to age-related disease. Cells get grumpy in old age In the 1960s, scientists discovered that cells can only divide a finite number of times – a number referred to as the Hayflick limit. Once you get to this point, however, a cell doesn’t die. Instead, it senesces – it enters a state in which it stops dividing and starts pumping out chemicals that cause damaging inflammation. Researchers are beginning to link senescence to a range of age-related diseases, including Alzheimer’s.

The skinny on heavy fat What is heavy fat? Fatty acids are made up of carbon, oxygen and hydrogen. To make a fatty acid, or any other hydrogen-containing molecule, “heavy”, hydrogen is swapped for its heavier isotope, deuterium. The result is a molecule that forms stronger bonds, and is more resistant to damage. Does heavy fat weigh more than normal fat? A little bit. An ice cube made of heavy water will sink in a glass of normal water. A mole – a standard unit used in chemistry – of the fatty linoleic acid weighs 280 grams, while a mole of heavy linoleic acid weighs 282 grams. Will eating heavy fat make me fatter? Not according to the researchers launching the heavy fat trial (see main story). The fatty acids they want to use as a substitute only make up 1 or 2 per cent of the total energy intake in a normal diet.

This article appeared in print under the headline “‘Heavy’ fat – the secret to eternal youth?”