‘Heavy’ fat – the secret to eternal youth?
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.
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. “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.”
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.”
Nenhum comentário:
Postar um comentário